Nadia Meyer, Katja Richter, Lars Brodowski, Constantin von Kaisenberg, Anette Melk, Bernhard Schmidt, Florian P. Limbourg, Bianca Schröder-Heurich, Frauke von Versen-Höynck
Objective
The long-term survival of kidney transplant patients has substantially improved. However, there is a higher risk for cardiovascular events after transplantation, partly due to immunosuppression. A diminished number of endothelial progenitor cells (EPCs), which play an important role in angiogenesis and the repair of endothelial damage, are associated with an increased cardiovascular risk. The aim of this study was to evaluate whether kidney transplantation affects EPCs in women.
Methods
Twenty-four healthy women and 22 female kidney transplant recipients were recruited. The ratio of angiogenic and non-angiogenic circulating progenitor cells (CPCs) was determined by multicolor flow cytometry and related to clinical parameters. Cord blood-derived endothelial colony-forming cells (ECFCs), a proliferative subgroup of endothelial progenitor cells, were treated with pooled sera from transplant patients or healthy controls and tested for their functional integrity using in vitro models.
Results
Kidney transplant recipients displayed a reduced ratio of angiogenic and non-angiogenic CPCs compared to healthy controls. Differences were especially pronounced in premenopausal women. Exposure to sera of transplanted women led to a significant impairment of ECFC proliferation, migration, and angiogenesis ability.
Conclusions
Alterations of EPC populations may contribute to the higher cardiovascular risks after organ transplantation and should be considered in therapeutic strategies.
{"title":"Impairment of endothelial progenitor cells in women after kidney transplantation","authors":"Nadia Meyer, Katja Richter, Lars Brodowski, Constantin von Kaisenberg, Anette Melk, Bernhard Schmidt, Florian P. Limbourg, Bianca Schröder-Heurich, Frauke von Versen-Höynck","doi":"10.1111/micc.12794","DOIUrl":"10.1111/micc.12794","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The long-term survival of kidney transplant patients has substantially improved. However, there is a higher risk for cardiovascular events after transplantation, partly due to immunosuppression. A diminished number of endothelial progenitor cells (EPCs), which play an important role in angiogenesis and the repair of endothelial damage, are associated with an increased cardiovascular risk. The aim of this study was to evaluate whether kidney transplantation affects EPCs in women.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twenty-four healthy women and 22 female kidney transplant recipients were recruited. The ratio of angiogenic and non-angiogenic circulating progenitor cells (CPCs) was determined by multicolor flow cytometry and related to clinical parameters. Cord blood-derived endothelial colony-forming cells (ECFCs), a proliferative subgroup of endothelial progenitor cells, were treated with pooled sera from transplant patients or healthy controls and tested for their functional integrity using in vitro models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Kidney transplant recipients displayed a reduced ratio of angiogenic and non-angiogenic CPCs compared to healthy controls. Differences were especially pronounced in premenopausal women. Exposure to sera of transplanted women led to a significant impairment of ECFC proliferation, migration, and angiogenesis ability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Alterations of EPC populations may contribute to the higher cardiovascular risks after organ transplantation and should be considered in therapeutic strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12794","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10602334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The lymphatic vascular system is crucial for optimizing body fluid level, regulating immune function, and transporting lipid. Relative to the experimental models to investigate blood vasculature, there are significantly fewer tools to explore lymphatics. Although in vivo studies have contributed to major discoveries in the field, finding and characterizing lymphatic specific markers has opened the door to isolating lymphatic vessels and cells for building ex vivo and in vitro platforms. These preparations have enabled the study and analysis of lymphatic vasculature in various physiological and pathophysiological conditions leading to a better understanding of cellular expressions and signaling. In this review, a broad range of ex vivo and in vitro engineered models are highlighted and categorized based on the major lymphatic function they model including contractile function, inflammation, drainage and immune regulation, lymphangiogenesis, and tumor-lymphatic interactions. Then, the novel 3D engineered tissues are introduced consisting of acellularized scaffolds and hydrogels to form vessels and cellular structures close to in vivo morphology. This paper also compares traditional in vitro methods with recent technologies and elaborates on the inherent advantages and limitations of each preparation by critically discussing simplest to most complex tissue-cellular structures. It concludes with an outlook of the lymphatic vasculature models and the possible future direction of contemporary tools, such as organ-on-chips.
{"title":"Engineered models of the lymphatic vascular system: Past, present, and future","authors":"Amirali Selahi, Abhishek Jain","doi":"10.1111/micc.12793","DOIUrl":"10.1111/micc.12793","url":null,"abstract":"<p>The lymphatic vascular system is crucial for optimizing body fluid level, regulating immune function, and transporting lipid. Relative to the experimental models to investigate blood vasculature, there are significantly fewer tools to explore lymphatics. Although in vivo studies have contributed to major discoveries in the field, finding and characterizing lymphatic specific markers has opened the door to isolating lymphatic vessels and cells for building ex vivo and in vitro platforms. These preparations have enabled the study and analysis of lymphatic vasculature in various physiological and pathophysiological conditions leading to a better understanding of cellular expressions and signaling. In this review, a broad range of ex vivo and in vitro engineered models are highlighted and categorized based on the major lymphatic function they model including contractile function, inflammation, drainage and immune regulation, lymphangiogenesis, and tumor-lymphatic interactions. Then, the novel 3D engineered tissues are introduced consisting of acellularized scaffolds and hydrogels to form vessels and cellular structures close to in vivo morphology. This paper also compares traditional in vitro methods with recent technologies and elaborates on the inherent advantages and limitations of each preparation by critically discussing simplest to most complex tissue-cellular structures. It concludes with an outlook of the lymphatic vasculature models and the possible future direction of contemporary tools, such as organ-on-chips.</p>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 2-3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9427243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We aneurysms based the in vascular endothelial cells triggers aneurysm development. Methods : We investigated the role of P2X4 purinoceptor, which is involved in flow- sensitive mechanisms in vascular endothelial cells, in the development of cerebral aneurysms by using the aneurysm-induced animal model. We also prospectively enrolled human patients with unruptured cerebral aneurysms, observed them for 3 years with cerebrovascular 3D imaging and carotid artery echo -cardiography, and compared the hemodynamic environments of the growth group with those of the non- growth group using computa-tional fluid dynamics (CFD) technique. Results : The incidence of cerebral aneurysms in aneurysm- induced P2X4 (−/−) mice was significantly lower than that in P2X4 (+/+) mice, and the incidence of cerebral aneurysms in aneurysm- induced rats treated with a P2X4 inhibitor, paroxetine was significantly lower than that in the non- treated group. Paroxetine treatment also significantly suppressed aneurysm growth. In the clinical study of human unruptured cerebral aneurysms, 461 patients were enrolled, and during the 3- year observation period, 38 aneurysms enlarged and 209 ones did not. In the CFD analysis, the magnitude of wall shear stress and transWSS, a metrics for shear stress disturbance, was significantly increased in the enlarged group, especially in the aneurysm neck. Normal brain function depends on stable cerebral blood flow and cerebral autoregulation. Cerebral blood flow is maintained even when blood pressure fluctuates. However, microcirculation in the cortex is not well understood when blood pressure drops rapidly. The purpose of this study was to determine oxyhemoglobin (O 2 Hb) changes, the indicator of cortical blood flow changes, during hypotension induced by thigh cuff release. Ten healthy students participated in this study. They were seated in a recumbent position in a quiet room. The cuffs of digital tourniquets were placed on both thighs and inflated to 250 mmHg for 5 min after 5 min rest, followed by deflation for 5 min. Right (R- ) and left (L- ) prefrontal cortex (PFC) O 2 Hb levels were measured using a multi- channel near- infrared spectroscopy system (LABNIRS; Shimadzu Co). O 2 Hb levels for each area were measured. Beat- to- beat mean arterial pressure (MAP) was recorded by volume clamping the finger pulse with a finger photoplethysmograph (Finometer; Finapres Medical Systems) on the left middle finger. O 2 Hb and MAP were averaged 1- sec epoch throughout the experi-ment. This study was approved by the Ethics Committee of Niigata University of Health and Welfare (18649- 210618). The decrease in MAP after the cuff release was 31.3 ± 5.6 mmHg. The decrease in O 2 Hb levels in the L- PFC (0.196 ± 0.088 mM∙cm) was larger than that in R- PFC (0.165 ± 0.072 mM∙cm) ( p < .05). These results suggest that the effect of hypotension induced by thigh cuff release on cortical blood flow might be different between cortical regions. Background : Pers
{"title":"Abstracts from the 47th Annual Meeting of Japanese Society for Microcirculation","authors":"","doi":"10.1111/micc.12784","DOIUrl":"10.1111/micc.12784","url":null,"abstract":"We aneurysms based the in vascular endothelial cells triggers aneurysm development. Methods : We investigated the role of P2X4 purinoceptor, which is involved in flow- sensitive mechanisms in vascular endothelial cells, in the development of cerebral aneurysms by using the aneurysm-induced animal model. We also prospectively enrolled human patients with unruptured cerebral aneurysms, observed them for 3 years with cerebrovascular 3D imaging and carotid artery echo -cardiography, and compared the hemodynamic environments of the growth group with those of the non- growth group using computa-tional fluid dynamics (CFD) technique. Results : The incidence of cerebral aneurysms in aneurysm- induced P2X4 (−/−) mice was significantly lower than that in P2X4 (+/+) mice, and the incidence of cerebral aneurysms in aneurysm- induced rats treated with a P2X4 inhibitor, paroxetine was significantly lower than that in the non- treated group. Paroxetine treatment also significantly suppressed aneurysm growth. In the clinical study of human unruptured cerebral aneurysms, 461 patients were enrolled, and during the 3- year observation period, 38 aneurysms enlarged and 209 ones did not. In the CFD analysis, the magnitude of wall shear stress and transWSS, a metrics for shear stress disturbance, was significantly increased in the enlarged group, especially in the aneurysm neck. Normal brain function depends on stable cerebral blood flow and cerebral autoregulation. Cerebral blood flow is maintained even when blood pressure fluctuates. However, microcirculation in the cortex is not well understood when blood pressure drops rapidly. The purpose of this study was to determine oxyhemoglobin (O 2 Hb) changes, the indicator of cortical blood flow changes, during hypotension induced by thigh cuff release. Ten healthy students participated in this study. They were seated in a recumbent position in a quiet room. The cuffs of digital tourniquets were placed on both thighs and inflated to 250 mmHg for 5 min after 5 min rest, followed by deflation for 5 min. Right (R- ) and left (L- ) prefrontal cortex (PFC) O 2 Hb levels were measured using a multi- channel near- infrared spectroscopy system (LABNIRS; Shimadzu Co). O 2 Hb levels for each area were measured. Beat- to- beat mean arterial pressure (MAP) was recorded by volume clamping the finger pulse with a finger photoplethysmograph (Finometer; Finapres Medical Systems) on the left middle finger. O 2 Hb and MAP were averaged 1- sec epoch throughout the experi-ment. This study was approved by the Ethics Committee of Niigata University of Health and Welfare (18649- 210618). The decrease in MAP after the cuff release was 31.3 ± 5.6 mmHg. The decrease in O 2 Hb levels in the L- PFC (0.196 ± 0.088 mM∙cm) was larger than that in R- PFC (0.165 ± 0.072 mM∙cm) ( p < .05). These results suggest that the effect of hypotension induced by thigh cuff release on cortical blood flow might be different between cortical regions. Background : Pers","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"29 8","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10438153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eleftheria Michalaki, Josephine M. Rudd, Lauren Liebman, Rahul Wadhwani, Levi B. Wood, Nick J. Willett, J. Brandon Dixon
Background
Dysfunction of the lymphatic system following injury, disease, or cancer treatment can lead to lymphedema, a debilitating condition with no cure. Despite the various physical therapy and surgical options available, most treatments are palliative and fail to address the underlying lymphatic vascular insufficiency driving lymphedema progression. Stem cell therapy provides a promising alternative in the treatment of various chronic diseases with a wide range of therapeutic effects that reduce inflammation, fibrosis, and oxidative stress, while promoting lymphatic vessel (LV) regeneration. Specifically, stem cell transplantation is suggested to promote LV restoration, rebuild lymphatic circulation, and thus potentially be utilized towards an effective lymphedema treatment. In addition to stem cells, studies have proposed the administration of vascular endothelial growth factor C (VEGFC) to promote lymphangiogenesis and decrease swelling in lymphedema.
Aims
Here, we seek to combine the benefits of stem cell therapy, which provides a cellular therapeutic approach that can respond to the tissue environment, and VEGFC administration to restore lymphatic drainage.
Materials & Methods
Specifically, we engineered mesenchymal stem cells (MSCs) to overexpress VEGFC using a lentiviral vector (hVEGFC MSC) and investigated their therapeutic efficacy in improving LV function and tissue swelling using near infrared (NIR) imaging, and lymphatic regeneration in a single LV ligation mouse tail lymphedema model.
Results
First, we showed that overexpression of VEGFC using lentiviral transduction led to an increase in VEGFC protein synthesis in vitro. Then, we demonstrated hVEGFC MSC administration post-injury significantly increased the lymphatic contraction frequency 14-, 21-, and 28-days post-surgery compared to the control animals (MSC administration) in vivo, while also reducing tail swelling 28-days post-surgery compared to controls.
Conclusion
Our results suggest a therapeutic potential of hVEGFC MSC in alleviating the lymphatic dysfunction observed during lymphedema progression after secondary injury and could provide a promising approach to enhancing autologous cell therapy for treating lymphedema.
{"title":"Lentiviral overexpression of VEGFC in transplanted MSCs leads to resolution of swelling in a mouse tail lymphedema model","authors":"Eleftheria Michalaki, Josephine M. Rudd, Lauren Liebman, Rahul Wadhwani, Levi B. Wood, Nick J. Willett, J. Brandon Dixon","doi":"10.1111/micc.12792","DOIUrl":"10.1111/micc.12792","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Dysfunction of the lymphatic system following injury, disease, or cancer treatment can lead to lymphedema, a debilitating condition with no cure. Despite the various physical therapy and surgical options available, most treatments are palliative and fail to address the underlying lymphatic vascular insufficiency driving lymphedema progression. Stem cell therapy provides a promising alternative in the treatment of various chronic diseases with a wide range of therapeutic effects that reduce inflammation, fibrosis, and oxidative stress, while promoting lymphatic vessel (LV) regeneration. Specifically, stem cell transplantation is suggested to promote LV restoration, rebuild lymphatic circulation, and thus potentially be utilized towards an effective lymphedema treatment. In addition to stem cells, studies have proposed the administration of vascular endothelial growth factor C (VEGFC) to promote lymphangiogenesis and decrease swelling in lymphedema.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Here, we seek to combine the benefits of stem cell therapy, which provides a cellular therapeutic approach that can respond to the tissue environment, and VEGFC administration to restore lymphatic drainage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials & Methods</h3>\u0000 \u0000 <p>Specifically, we engineered mesenchymal stem cells (MSCs) to overexpress VEGFC using a lentiviral vector (hVEGFC MSC) and investigated their therapeutic efficacy in improving LV function and tissue swelling using near infrared (NIR) imaging, and lymphatic regeneration in a single LV ligation mouse tail lymphedema model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>First, we showed that overexpression of VEGFC using lentiviral transduction led to an increase in VEGFC protein synthesis in vitro. Then, we demonstrated hVEGFC MSC administration post-injury significantly increased the lymphatic contraction frequency 14-, 21-, and 28-days post-surgery compared to the control animals (MSC administration) in vivo, while also reducing tail swelling 28-days post-surgery compared to controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results suggest a therapeutic potential of hVEGFC MSC in alleviating the lymphatic dysfunction observed during lymphedema progression after secondary injury and could provide a promising approach to enhancing autologous cell therapy for treating lymphedema.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 2-3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9803358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lymphatic vessels collect interstitial fluid, immune cells, and digested lipids and return these bodily fluids to blood through two pairs of lymphovenous valves (LVVs). Like other cardiovascular valves LVVs prevent the backflow of blood into the lymphatic vessels. In addition to LVVs, platelets are necessary to prevent the entry of blood into the lymphatic vessels. Platelet thrombi are observed at LVVs suggesting that LVVs and platelets function in synergy to regulate blood/lymphatic separation.
Objectives
The primary objective of this work is to determine whether platelets can regulate blood/lymph separation independently of LVVs.
Methods
The transcription factor GATA2 is necessary for the development of both LVVs and hematopoietic stem cells. Using various endothelial- and hematopoietic cell expressed Cre-lines, we conditionally deleted Gata2. We hypothesized that this strategy would identify the tissue- and time-specific roles of GATA2 and reveal whether platelets and LVVs can independently regulate blood/lymph separation.
Results
Lymphatic vasculature-specific deletion of Gata2 results in the absence of LVVs without compromising blood/lymph separation. In contrast, deletion of GATA2 from both lymphatic vasculature and hematopoietic cells results in the absence of LVVs, reduced number of platelets and blood-filled lymphatic vasculature.
Conclusion
GATA2 promotes blood/lymph separation through platelets. Furthermore, LVVs are the only known sites of interaction between blood and lymphatic vessels. The fact that blood is able to enter the lymphatic vessels of mice lacking LVVs and platelets indicates that under these circumstances the lymphatic and blood vessels are connected at yet to be identified sites.
{"title":"GATA2 regulates blood/lymph separation in a platelet-dependent and lymphovenous valve-independent manner","authors":"Md. Riaj Mahamud, Xin Geng, Lijuan Chen, Zoheb Ahmed, Yenchun Ho, R. Sathish Srinivasan","doi":"10.1111/micc.12787","DOIUrl":"10.1111/micc.12787","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Lymphatic vessels collect interstitial fluid, immune cells, and digested lipids and return these bodily fluids to blood through two pairs of lymphovenous valves (LVVs). Like other cardiovascular valves LVVs prevent the backflow of blood into the lymphatic vessels. In addition to LVVs, platelets are necessary to prevent the entry of blood into the lymphatic vessels. Platelet thrombi are observed at LVVs suggesting that LVVs and platelets function in synergy to regulate blood/lymphatic separation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The primary objective of this work is to determine whether platelets can regulate blood/lymph separation independently of LVVs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The transcription factor GATA2 is necessary for the development of both LVVs and hematopoietic stem cells. Using various endothelial- and hematopoietic cell expressed Cre-lines, we conditionally deleted Gata2. We hypothesized that this strategy would identify the tissue- and time-specific roles of GATA2 and reveal whether platelets and LVVs can independently regulate blood/lymph separation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Lymphatic vasculature-specific deletion of Gata2 results in the absence of LVVs without compromising blood/lymph separation. In contrast, deletion of GATA2 from both lymphatic vasculature and hematopoietic cells results in the absence of LVVs, reduced number of platelets and blood-filled lymphatic vasculature.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>GATA2 promotes blood/lymph separation through platelets. Furthermore, LVVs are the only known sites of interaction between blood and lymphatic vessels. The fact that blood is able to enter the lymphatic vessels of mice lacking LVVs and platelets indicates that under these circumstances the lymphatic and blood vessels are connected at yet to be identified sites.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 2-3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12787","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9489317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Annalinda Pisano, Loredana Le Pera, Raffaella Carletti, Bruna Cerbelli, Maria G. Pignataro, Angelina Pernazza, Fabrizio Ferre, Maria Lombardi, Davide Lazzeroni, Iacopo Olivotto, Ornella E. Rimoldi, Chiara Foglieni, Paolo G. Camici, Giulia d'Amati
Objective
Coronary microvascular dysfunction (CMD) is a key pathophysiological feature of hypertrophic cardiomyopathy (HCM), contributing to myocardial ischemia and representing a critical determinant of patients' adverse outcome. The molecular mechanisms underlying the morphological and functional changes of CMD are still unknown. Aim of this study was to obtain insights on the molecular pathways associated with microvessel remodeling in HCM.
Methods
Interventricular septum myectomies from patients with obstructive HCM (n = 20) and donors' hearts (CTRL, discarded for technical reasons, n = 7) were collected. Remodeled intramyocardial arterioles and cardiomyocytes were microdissected by laser capture and next-generation sequencing was used to delineate the transcriptome profile.
Results
We identified 720 exclusive differentially expressed genes (DEGs) in cardiomyocytes and 1315 exclusive DEGs in remodeled arterioles of HCM. Performing gene ontology and pathway enrichment analyses, we identified selectively altered pathways between remodeled arterioles and cardiomyocytes in HCM patients and controls.
Conclusions
We demonstrate the existence of distinctive pathways between remodeled arterioles and cardiomyocytes in HCM patients and controls at the transcriptome level.
{"title":"RNA-seq profiling reveals different pathways between remodeled vessels and myocardium in hypertrophic cardiomyopathy","authors":"Annalinda Pisano, Loredana Le Pera, Raffaella Carletti, Bruna Cerbelli, Maria G. Pignataro, Angelina Pernazza, Fabrizio Ferre, Maria Lombardi, Davide Lazzeroni, Iacopo Olivotto, Ornella E. Rimoldi, Chiara Foglieni, Paolo G. Camici, Giulia d'Amati","doi":"10.1111/micc.12790","DOIUrl":"10.1111/micc.12790","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Coronary microvascular dysfunction (CMD) is a key pathophysiological feature of hypertrophic cardiomyopathy (HCM), contributing to myocardial ischemia and representing a critical determinant of patients' adverse outcome. The molecular mechanisms underlying the morphological and functional changes of CMD are still unknown. Aim of this study was to obtain insights on the molecular pathways associated with microvessel remodeling in HCM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Interventricular septum myectomies from patients with obstructive HCM (<i>n</i> = 20) and donors' hearts (CTRL, discarded for technical reasons, <i>n</i> = 7) were collected. Remodeled intramyocardial arterioles and cardiomyocytes were microdissected by laser capture and next-generation sequencing was used to delineate the transcriptome profile.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 720 exclusive differentially expressed genes (DEGs) in cardiomyocytes and 1315 exclusive DEGs in remodeled arterioles of HCM. Performing gene ontology and pathway enrichment analyses, we identified selectively altered pathways between remodeled arterioles and cardiomyocytes in HCM patients and controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We demonstrate the existence of distinctive pathways between remodeled arterioles and cardiomyocytes in HCM patients and controls at the transcriptome level.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"29 8","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9787970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10447526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michiko Jo, Andrea N. Trujillo, Naotoshi Shibahara, Jerome W. Breslin
Background
Goreisan is a traditional herbal formulation with diuretic properties tested as a clinical therapeutic to alleviate lymphedema in Japan. The present study aimed to determine how Goreisan and its five different components affect lymphatic pump function.
Methods
Mesenteric collecting lymphatics were isolated from anesthetized Sprague–Dawley rats and mounted on resistance-matched glass micropipettes in a 37°C physiological salt solution bath for studies. Diameter was continuously measured to obtain the following lymphatic pump parameters: contraction frequency (CF), end diastolic diameter (EDD), and end systolic diameter (ESD), contraction amplitude (AMP), ejection fraction (EF), and fractional pump flow (FPF). Goreisan and each of its components (Cinnamomi Cortex, Atractylodis Rhizoma, Alismatis Rhizoma, Polyporus, and Poria) were applied to the bath at concentrations of 1–30 μg/mL.
Results
The results show that while Goreisan causes no significant changes to lymphatic pumping, Alismatis Rhizoma and Polyporus each significantly reduce CF and FPF. In addition, rats that received oral administration of Goreisan and Alismatis Rhizoma for 1 week had elevated expression of VEGFR-3 in their mesenteric collecting lymphatics.
Conclusions
Collectively, the results suggest that some components of Goreisan have a direct, rapid impact on lymphatic pumping. These findings provide new insights but also raise new questions about the therapeutic potential of Goreisan in patients with secondary lymphedema.
{"title":"Impact of Goreisan components on rat mesenteric collecting lymphatic vessel pumping","authors":"Michiko Jo, Andrea N. Trujillo, Naotoshi Shibahara, Jerome W. Breslin","doi":"10.1111/micc.12788","DOIUrl":"10.1111/micc.12788","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Goreisan is a traditional herbal formulation with diuretic properties tested as a clinical therapeutic to alleviate lymphedema in Japan. The present study aimed to determine how Goreisan and its five different components affect lymphatic pump function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Mesenteric collecting lymphatics were isolated from anesthetized Sprague–Dawley rats and mounted on resistance-matched glass micropipettes in a 37°C physiological salt solution bath for studies. Diameter was continuously measured to obtain the following lymphatic pump parameters: contraction frequency (CF), end diastolic diameter (EDD), and end systolic diameter (ESD), contraction amplitude (AMP), ejection fraction (EF), and fractional pump flow (FPF). Goreisan and each of its components (Cinnamomi Cortex, Atractylodis Rhizoma, Alismatis Rhizoma, Polyporus, and Poria) were applied to the bath at concentrations of 1–30 μg/mL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results show that while Goreisan causes no significant changes to lymphatic pumping, Alismatis Rhizoma and Polyporus each significantly reduce CF and FPF. In addition, rats that received oral administration of Goreisan and Alismatis Rhizoma for 1 week had elevated expression of VEGFR-3 in their mesenteric collecting lymphatics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Collectively, the results suggest that some components of Goreisan have a direct, rapid impact on lymphatic pumping. These findings provide new insights but also raise new questions about the therapeutic potential of Goreisan in patients with secondary lymphedema.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 2-3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12788","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9803328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NLRP3 inflammasome mediates myocardial ischemia/reperfusion (MI/R) injury and diabetic vascular endothelia dysfunction. However, the role of NLRP3 inflammasome in MI/R injury with diabetes has not been fully described. Irisin plays an important role in anti-inflammation and improves endothelial function in type 2 diabetes. The current study aimed to investigate the effect of irisin on regulating NLRP3 inflammasome activation in diabetic vascular endothelia dysfunction.
Methods
Cardiac microvascular endothelial cells (CMECs) were cultured and subjected to high glucose/high fat (HG/HF) receiving hypoxia/reoxygenation (H/R) with irisin incubation or not. Then, apoptosis, viability, migration, NO secretion, and inflammasome activation were examined.
Results
The hypoxic CMECs exhibited increased apoptosis, impaired viability, and migration, even decreased NO secretion and enhanced inflammasome activation. Moreover, irisin incubation decreased NLRP3 activation and attenuated cell injury in HG/HF cultured CMECs subjected to H/R injury, which was abolished by NLRP3 inflammasome activation. Meanwhile, NLRP3 inflammasome siRNA also attenuated H/R injury in CMECs under HG/HF condition.
Conclusion
The current study demonstrated for the first time that irisin inhibits NLRP3 inflammasome activation in CMECs as a novel mechanism in myocardial ischemia/reperfusion injury in diabetes.
{"title":"Irisin inhibits NLRP3 inflammasome activation in HG/HF incubated cardiac microvascular endothelial cells with H/R injury","authors":"Chao Xin, Jinglong Zhang, Ningbo Hao, Jianan Wang, Hui Liu, Hanwen Wei, Yong Wang, Chengzhu Wang, Shuo Wang, Chengrong Zheng, Zheng Zhang, Zhitao Jin","doi":"10.1111/micc.12786","DOIUrl":"10.1111/micc.12786","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>NLRP3 inflammasome mediates myocardial ischemia/reperfusion (MI/R) injury and diabetic vascular endothelia dysfunction. However, the role of NLRP3 inflammasome in MI/R injury with diabetes has not been fully described. Irisin plays an important role in anti-inflammation and improves endothelial function in type 2 diabetes. The current study aimed to investigate the effect of irisin on regulating NLRP3 inflammasome activation in diabetic vascular endothelia dysfunction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Cardiac microvascular endothelial cells (CMECs) were cultured and subjected to high glucose/high fat (HG/HF) receiving hypoxia/reoxygenation (H/R) with irisin incubation or not. Then, apoptosis, viability, migration, NO secretion, and inflammasome activation were examined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The hypoxic CMECs exhibited increased apoptosis, impaired viability, and migration, even decreased NO secretion and enhanced inflammasome activation. Moreover, irisin incubation decreased NLRP3 activation and attenuated cell injury in HG/HF cultured CMECs subjected to H/R injury, which was abolished by NLRP3 inflammasome activation. Meanwhile, NLRP3 inflammasome siRNA also attenuated H/R injury in CMECs under HG/HF condition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The current study demonstrated for the first time that irisin inhibits NLRP3 inflammasome activation in CMECs as a novel mechanism in myocardial ischemia/reperfusion injury in diabetes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"29 8","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10447756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Over the last century, scientific discoveries have revealed the critical role of the microcirculation in maintaining homeostasis and the etiology of diseases ranging from cancer to COVID-19. These advances have coincided with and even been made possible by the exponential progress in imaging and visualization techniques capable of characterizing the structural and functional diversity of the microcirculation. Consequently, this special issue (SI) showcases a broad selection of tools and methods for elucidating the role of the microcirculation in health and disease. In this exciting compendium of globally contributed articles, authors investigate in vitro and in vivo models, describe new imaging methods spanning from the endothelial cell to the whole organ scale, as well as analytical approaches focused on the microvascular and lymphatic systems. Also included are articles describing the use of ultrasound and photoacoustic imaging of the microcirculation in the clinical and preclinical realms. We believe this SI on "Visualizing the Microcirculation" contains something for everyone, from basic scientists to clinicians interested in the microcirculation.
{"title":"Visualizing the Microcirculation","authors":"Janaka Senarathna, Arvind P. Pathak","doi":"10.1111/micc.12785","DOIUrl":"10.1111/micc.12785","url":null,"abstract":"Over the last century, scientific discoveries have revealed the critical role of the microcirculation in maintaining homeostasis and the etiology of diseases ranging from cancer to COVID-19. These advances have coincided with and even been made possible by the exponential progress in imaging and visualization techniques capable of characterizing the structural and functional diversity of the microcirculation. Consequently, this special issue (SI) showcases a broad selection of tools and methods for elucidating the role of the microcirculation in health and disease. In this exciting compendium of globally contributed articles, authors investigate in vitro and in vivo models, describe new imaging methods spanning from the endothelial cell to the whole organ scale, as well as analytical approaches focused on the microvascular and lymphatic systems. Also included are articles describing the use of ultrasound and photoacoustic imaging of the microcirculation in the clinical and preclinical realms. We believe this SI on \"Visualizing the Microcirculation\" contains something for everyone, from basic scientists to clinicians interested in the microcirculation.","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"29 6-7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10447497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peng Hu, Bochao Niu, Hang Yang, Yang Xia, Donna Chen, Chun Meng, Ke Chen, Bharat Biswal
Background
Previous studies have used regional cerebral blood flow (CBF) hemodynamic response to measure brain activities. In this work, we use a laser speckle contrast imaging (LSCI) apparatus to sample the CBF activation in somatosensory cortex (S1BF) with repetitive whisker stimulation. Traditionally, the CBF activations were processed by depicting the change percentage above baseline; however, it is not clear how different methods influence the detection of activations.
Aims
Thus, in this work we investigate the influence of different methods to detect activations in LSCI.
Materials & Methods
First, principal component analysis (PCA) was performed to denoise the CBF signal. As the signal of the first principal component (PC1) showed the highest correlation with the S1BF CBF response curve, PC1 was used in the subsequent analyses. Then, we used fast Fourier transform (FFT) to evaluate the frequency properties of the LSCI images and the activation map was generated based on the amplitude of the central frequency. Furthermore, Pearson's correlation coefficient (C–C) analysis and a general linear model (GLM) were performed to estimate the S1BF activation based on the time series of PC1.
Results
We found that GLM performed better in identifying activation than C–C. Additionally, the activation maps generated by FFT were similar to those obtained by GLM. Particularly, the superficial vein and arterial vessels separated the activation region as segmented activated areas, and the regions with unresolved vessels showed a common activation for whisker stimulation.
Discussion and Conclusion
Our research analyzed the extent to which PCA can extract meaningful information from the signal and we compared the performance for detecting brain functional activation between different methods that rely on LSCI. This can be used as a reference for LSCI researchers on choosing the best method to estimate brain activation.
{"title":"Analysis and visualization methods for detecting functional activation using laser speckle contrast imaging","authors":"Peng Hu, Bochao Niu, Hang Yang, Yang Xia, Donna Chen, Chun Meng, Ke Chen, Bharat Biswal","doi":"10.1111/micc.12783","DOIUrl":"10.1111/micc.12783","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Previous studies have used regional cerebral blood flow (CBF) hemodynamic response to measure brain activities. In this work, we use a laser speckle contrast imaging (LSCI) apparatus to sample the CBF activation in somatosensory cortex (S1BF) with repetitive whisker stimulation. Traditionally, the CBF activations were processed by depicting the change percentage above baseline; however, it is not clear how different methods influence the detection of activations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Thus, in this work we investigate the influence of different methods to detect activations in LSCI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials & Methods</h3>\u0000 \u0000 <p>First, principal component analysis (PCA) was performed to denoise the CBF signal. As the signal of the first principal component (PC1) showed the highest correlation with the S1BF CBF response curve, PC1 was used in the subsequent analyses. Then, we used fast Fourier transform (FFT) to evaluate the frequency properties of the LSCI images and the activation map was generated based on the amplitude of the central frequency. Furthermore, Pearson's correlation coefficient (C–C) analysis and a general linear model (GLM) were performed to estimate the S1BF activation based on the time series of PC1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that GLM performed better in identifying activation than C–C. Additionally, the activation maps generated by FFT were similar to those obtained by GLM. Particularly, the superficial vein and arterial vessels separated the activation region as segmented activated areas, and the regions with unresolved vessels showed a common activation for whisker stimulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion and Conclusion</h3>\u0000 \u0000 <p>Our research analyzed the extent to which PCA can extract meaningful information from the signal and we compared the performance for detecting brain functional activation between different methods that rely on LSCI. This can be used as a reference for LSCI researchers on choosing the best method to estimate brain activation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"29 6-7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10793553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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