Myocardial infarction (MI) with resulting congestive heart failure is one of the leading causes of death worldwide. Current therapies for treating MI, such as devices, traditional medicine, and surgeries, come with many limitations as patients in their final stages of heart failure have little chances of experiencing any reversible changes. In recent decades, Mesenchymal stem cell (MSC) based therapy has become one of the most popular and rapidly developing fields in treating MI. Their supremacy for clinical applications is partially due to their unique properties and encouraging pre-clinical outcomes in various animal disease models. However, the majority of clinical trials registered for MSC therapy for diverse human diseases, including MI, have fallen short of expectations. This review intends to discuss the recent advances in the clinical application of using MSCs for cardiac repair and discuss challenges facing the clinical translation of MSCs for cardiac regeneration such as restoration of endothelial-cardiomyocyte crosstalk, immunomodulation and immune rejection, poor homing and migration, as well as low retention and survival. Furthermore, we will discuss recent strategies being investigated to help overcome some of these challenges.
{"title":"Clinical translation of mesenchymal stem cells in ischemic heart failure: Challenges and future perspectives","authors":"Anqi Guan , Lisa Alibrandi , Elika Verma , Niketa Sareen , Qingdong Guan , Vincenzo Lionetti , Sanjiv Dhingra","doi":"10.1016/j.vph.2025.107491","DOIUrl":"10.1016/j.vph.2025.107491","url":null,"abstract":"<div><div>Myocardial infarction (MI) with resulting congestive heart failure is one of the leading causes of death worldwide. Current therapies for treating MI, such as devices, traditional medicine, and surgeries, come with many limitations as patients in their final stages of heart failure have little chances of experiencing any reversible changes. In recent decades, Mesenchymal stem cell (MSC) based therapy has become one of the most popular and rapidly developing fields in treating MI. Their supremacy for clinical applications is partially due to their unique properties and encouraging pre-clinical outcomes in various animal disease models. However, the majority of clinical trials registered for MSC therapy for diverse human diseases, including MI, have fallen short of expectations. This review intends to discuss the recent advances in the clinical application of using MSCs for cardiac repair and discuss challenges facing the clinical translation of MSCs for cardiac regeneration such as restoration of endothelial-cardiomyocyte crosstalk, immunomodulation and immune rejection, poor homing and migration, as well as low retention and survival. Furthermore, we will discuss recent strategies being investigated to help overcome some of these challenges.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"159 ","pages":"Article 107491"},"PeriodicalIF":3.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cardiovascular diseases remain the leading cause of disability and death in the Western world. Effective cardioprotection involves limiting ischemia/reperfusion injury (IRI), including cell death (pyroptosis) driven by the NLRP3 inflammasome. While various cardiac resident cellular populations contribute to cardioprotection, it remains unclear whether targeting resident macrophages is inherently cardioprotective. Given that INF150, an NLRP3 inhibitor, exhibits varying abilities to penetrate cardiomyocytes and macrophages, we sought to address this question.
Methods
We studied the cardioprotective potential of INF150, the potent metabolite of the NLRP3 inhibitor INF195, in isolated hearts or cells. In isolated hearts, we measured infarct size, caspase-1 cleavage, and interleukins (IL) release, while in macrophages, naïve H9c2 and differentiated H9c2 cells, we analyzed cell viability, and pyroptosis markers, including IL-1β release and Gasdermin D cleavage, following hypoxia/reoxygenation (H/R).
Results and conclusion
While INF150 effectively shielded macrophages from LPS/ATP challenges, it failed to penetrate H9c2 and differentiated H9c2, even at high concentrations (no changes in pyroptosis markers induced by H/R). In the isolated mice heart model, INF150 did not demonstrate cardioprotective effects: infarct size, IL-1β, cleaved caspase-1 levels did not change significantly across tested concentrations of INF150. These findings suggest that while INF150 shows promise in macrophage/phagocytic models, its inability to penetrate cardiomyocytes limits its effectiveness in the whole cardiac tissue. Our results underscore the importance of cardiomyocyte uptake for effective cardioprotection, highlighting the need for NLRP3 inhibitors capable of targeting these cells directly. Future research should focus on enhancing the delivery and cardiomyocyte uptake of NLRP3 inhibitors to achieve cardioprotection. Unlike its precursor, INF195, which penetrates H9c2 cells, INF150 does not appear to offer cardioprotection in the whole organ.
{"title":"Macrophage and cardiomyocyte roles in cardioprotection: Exploiting the NLRP3 Inflammasome inhibitor INF150","authors":"Magalì Giordano , Saveria Femminò , Federica Blua , Francesca Boccato , Chiara Rubeo , Beatrice Mantuano , Francesca Cioffi , Stefano Comità , Arianna Brovero , Rosa Ciullo , Massimo Bertinaria , Claudia Penna , Pasquale Pagliaro","doi":"10.1016/j.vph.2025.107487","DOIUrl":"10.1016/j.vph.2025.107487","url":null,"abstract":"<div><h3>Background</h3><div>Cardiovascular diseases remain the leading cause of disability and death in the Western world. Effective cardioprotection involves limiting ischemia/reperfusion injury (IRI), including cell death (pyroptosis) driven by the NLRP3 inflammasome. While various cardiac resident cellular populations contribute to cardioprotection, it remains unclear whether targeting resident macrophages is inherently cardioprotective. Given that INF150, an NLRP3 inhibitor, exhibits varying abilities to penetrate cardiomyocytes and macrophages, we sought to address this question.</div></div><div><h3>Methods</h3><div>We studied the cardioprotective potential of INF150, the potent metabolite of the NLRP3 inhibitor INF195, in isolated hearts or cells. In isolated hearts, we measured infarct size, caspase-1 cleavage, and interleukins (IL) release, while in macrophages, naïve H9c2 and differentiated H9c2 cells, we analyzed cell viability, and pyroptosis markers, including IL-1β release and Gasdermin D cleavage, following hypoxia/reoxygenation (H/R).</div></div><div><h3>Results and conclusion</h3><div>While INF150 effectively shielded macrophages from LPS/ATP challenges, it failed to penetrate H9c2 and differentiated H9c2, even at high concentrations (no changes in pyroptosis markers induced by H/R). In the isolated mice heart model, INF150 did not demonstrate cardioprotective effects: infarct size, IL-1β, cleaved caspase-1 levels did not change significantly across tested concentrations of INF150. These findings suggest that while INF150 shows promise in macrophage/phagocytic models, its inability to penetrate cardiomyocytes limits its effectiveness in the whole cardiac tissue. Our results underscore the importance of cardiomyocyte uptake for effective cardioprotection, highlighting the need for NLRP3 inhibitors capable of targeting these cells directly. Future research should focus on enhancing the delivery and cardiomyocyte uptake of NLRP3 inhibitors to achieve cardioprotection. Unlike its precursor, INF195, which penetrates H9c2 cells, INF150 does not appear to offer cardioprotection in the whole organ.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"159 ","pages":"Article 107487"},"PeriodicalIF":3.5,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-15DOI: 10.1016/j.vph.2025.107490
Bianca E. Suur , Glykeria Karadimou , Colin J.J.M. Willems , Otto Bergman , Mariette Lengquist , Malin Kronqvist , Roland Baumgartner , Stephen Malin , Anton Gisterå , Göran K. Hansson , Anders Mälarstig , Ulf Hedin , Daniel F.J. Ketelhuth , Ljubica Matic
Background
Proprotein convertase subtilisins/kexins (PCSKs) have been implicated in cancers and cardiovascular disease. We have shown that PCSK6 is a key protease regulating smooth muscle cell (SMC)-mediated vascular remodeling, but also that it can be expressed by T cells and macrophages in atherosclerotic plaques. Whether PCSK6 regulates innate and adaptive immune responses in the context of vascular inflammation is still unknown.
Methods
In this study, detailed immunophenotyping of constitutive Pcsk6−/− mice was performed. Bone marrow transplantation into high-cholesterol diet fed Ldlr−/− mice was used to investigate PCSK6-mediated immune effects in atherogenesis and plaque stability.
Results
Compared to controls, Pcsk6−/− mice showed higher plasma levels of the chemoattractants CCL2 and CCCL3, and Th17 cytokines IL-17 A and IL-17F. Pcsk6 ablation led to increased naïve and effector-memory CD4+ and CD8+ cell numbers in the spleen, and increased release of IL-17 A, IFN-γ and IL-10 as well as proliferation by spleenocytes in vitro. Lack of Pcsk6 also affected innate immunity as macrophages from Pcsk6−/− mice secreted more cytokines, including TNF-α, CCL2, IL-6 and IL-10 upon LPS stimulation in vitro, and were more prone to oxLDL uptake. In line with a pro-inflammatory phenotype, Pcsk6−/−➔Ldlr−/− transplanted mice presented a higher atherosclerotic plaque burden compared to Ldlr−/− receiving control bone marrow. Although larger, Pcsk6−/−➔Ldlr−/− plaques showed increased stability features, including collagen deposition and SMC presence coinciding with significantly increased local levels of the fibrogenic cytokine IL-17.
Conclusions
Global Pcsk6 ablation leads to the activation of both adaptive and innate immune systems. Interestingly, Pcsk6−/− ablation in bone marrow of hyperlipidemic mice revealed its dual role in atherogenesis, activating a Th17-SMC modulatory axis that promotes plaque stability, despite increased atherosclerotic burden.
{"title":"PCSK6 ablation in blood circulating cells increases atherosclerotic burden, but improves plaque stability by activating Th17-smooth muscle cell modulatory axis","authors":"Bianca E. Suur , Glykeria Karadimou , Colin J.J.M. Willems , Otto Bergman , Mariette Lengquist , Malin Kronqvist , Roland Baumgartner , Stephen Malin , Anton Gisterå , Göran K. Hansson , Anders Mälarstig , Ulf Hedin , Daniel F.J. Ketelhuth , Ljubica Matic","doi":"10.1016/j.vph.2025.107490","DOIUrl":"10.1016/j.vph.2025.107490","url":null,"abstract":"<div><h3>Background</h3><div>Proprotein convertase subtilisins/kexins (PCSKs) have been implicated in cancers and cardiovascular disease. We have shown that PCSK6 is a key protease regulating smooth muscle cell (SMC)-mediated vascular remodeling, but also that it can be expressed by T cells and macrophages in atherosclerotic plaques. Whether PCSK6 regulates innate and adaptive immune responses in the context of vascular inflammation is still unknown.</div></div><div><h3>Methods</h3><div>In this study, detailed immunophenotyping of constitutive <em>Pcsk6</em><sup><em>−/−</em></sup> mice was performed. Bone marrow transplantation into high-cholesterol diet fed <em>Ldlr</em><sup><em>−/−</em></sup> mice was used to investigate PCSK6-mediated immune effects in atherogenesis and plaque stability.</div></div><div><h3>Results</h3><div>Compared to controls, <em>Pcsk6</em><sup><em>−/−</em></sup> mice showed higher plasma levels of the chemoattractants CCL2 and CCCL3, and Th17 cytokines IL-17 A and IL-17F<em>. Pcsk6</em> ablation led to increased naïve and effector-memory CD4+ and CD8+ cell numbers in the spleen, and increased release of IL-17 A, IFN-γ and IL-10 as well as proliferation by spleenocytes <em>in vitro</em>. Lack of Pcsk6 also affected innate immunity as macrophages from <em>Pcsk6</em><sup><em>−/−</em></sup> mice secreted more cytokines, including TNF-α, CCL2, IL-6 and IL-10 upon LPS stimulation <em>in vitro</em>, and were more prone to oxLDL uptake. In line with a pro-inflammatory phenotype, <em>Pcsk6</em><sup><em>−/−</em></sup>➔<em>Ldlr</em><sup><em>−/−</em></sup> transplanted mice presented a higher atherosclerotic plaque burden compared to <em>Ldlr</em><sup><em>−/−</em></sup> receiving control bone marrow. Although larger, <em>Pcsk6</em><sup><em>−/−</em></sup>➔<em>Ldlr</em><sup><em>−/−</em></sup> plaques showed increased stability features, including collagen deposition and SMC presence coinciding with significantly increased local levels of the fibrogenic cytokine IL-17.</div></div><div><h3>Conclusions</h3><div>Global <em>Pcsk6</em> ablation leads to the activation of both adaptive and innate immune systems. Interestingly, <em>Pcsk6</em><sup><em>−/−</em></sup> ablation in bone marrow of hyperlipidemic mice revealed its dual role in atherogenesis, activating a Th17-SMC modulatory axis that promotes plaque stability, despite increased atherosclerotic burden.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"159 ","pages":"Article 107490"},"PeriodicalIF":3.5,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-15DOI: 10.1016/j.vph.2025.107488
Maia Lyall , Anna Kamdar , Robert Sykes , Badri L. Aekbote , Nikolaj Gadegaard , Colin Berry
Vascular smooth muscle cell (VSMC) contractility mediates blood vessel tone. Abnormalities in VSMC function and in blood vessel tone can contribute to a variety of cardiovascular diseases. This review examines the role of VSMC contractile force in vascular disease, divided into two primary sections. The first section introducing VSMC mechanical contraction and detailing the molecular mechanisms of VSMC contractility in normal and pathological states. The second section exploring methods of measuring contraction in VSMCs, such as Ca2+ imaging, myography, and traction force microscopy, and highlighting where each method is of best use. Understanding the mechanical properties and contractile profiles of VSMCs offers valuable insights into disease mechanisms. By investigating these aspects, this review describes the potential of VSMC contractile forces as diagnostic markers and therapeutic targets in vascular disease.
{"title":"Measuring contractile forces in vascular smooth muscle cells","authors":"Maia Lyall , Anna Kamdar , Robert Sykes , Badri L. Aekbote , Nikolaj Gadegaard , Colin Berry","doi":"10.1016/j.vph.2025.107488","DOIUrl":"10.1016/j.vph.2025.107488","url":null,"abstract":"<div><div>Vascular smooth muscle cell (VSMC) contractility mediates blood vessel tone. Abnormalities in VSMC function and in blood vessel tone can contribute to a variety of cardiovascular diseases. This review examines the role of VSMC contractile force in vascular disease, divided into two primary sections. The first section introducing VSMC mechanical contraction and detailing the molecular mechanisms of VSMC contractility in normal and pathological states. The second section exploring methods of measuring contraction in VSMCs, such as Ca<sup>2+</sup> imaging, myography, and traction force microscopy, and highlighting where each method is of best use. Understanding the mechanical properties and contractile profiles of VSMCs offers valuable insights into disease mechanisms. By investigating these aspects, this review describes the potential of VSMC contractile forces as diagnostic markers and therapeutic targets in vascular disease.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"159 ","pages":"Article 107488"},"PeriodicalIF":3.5,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-15DOI: 10.1016/j.vph.2025.107489
I. Fancello , S. Willett , C. Castiglioni , S. Amer , S. Santoleri , L. Bragg , F. Galli , G. Cossu
Objective
During growth and differentiation of skeletal muscle, cell types other than canonical myoblasts can be recruited to a myogenic fate. Among these, TNAP+ pericytes can differentiate into skeletal or smooth muscle cells during postnatal growth and contribute to muscle regeneration. However, their role in muscle development has not been investigated. This study aims to characterise pericyte fate choices during embryonic and foetal myogenesis, occurring in the second half of gestation.
Approach and results
Using Cre-loxP lineage tracing with multiple reporters including the multifluorescent Confetti, we labelled TNAP+ precursors in vivo and assessed the smooth or skeletal muscle differentiation in their lineage at a perinatal stage. We found that TNAP+ cells contribute in vivo to skeletal and smooth muscle cells, as well as other pericytes, also during pre-natal muscle development. The resulting clones showed that such fate choices are likely to depend on distinct unipotent progenitors rather than multipotent progenitors. In addition, we isolated and differentiated in vitro foetal cells derived from TNAP+ precursors, which showed that they are not spontaneously myogenic unless co-cultured with other skeletal muscle cells.
Conclusions
This work extends our understanding of the differentiative potency of these non- canonical skeletal muscle progenitors during prenatal life, with a view to a future application of this knowledge to optimise cell therapies for muscle wasting disorders.
{"title":"TNAP expressing adventitial pericytes contribute to myogenesis during foetal development","authors":"I. Fancello , S. Willett , C. Castiglioni , S. Amer , S. Santoleri , L. Bragg , F. Galli , G. Cossu","doi":"10.1016/j.vph.2025.107489","DOIUrl":"10.1016/j.vph.2025.107489","url":null,"abstract":"<div><h3>Objective</h3><div>During growth and differentiation of skeletal muscle, cell types other than canonical myoblasts can be recruited to a myogenic fate. Among these, TNAP+ pericytes can differentiate into skeletal or smooth muscle cells during postnatal growth and contribute to muscle regeneration. However, their role in muscle development has not been investigated. This study aims to characterise pericyte fate choices during embryonic and foetal myogenesis, occurring in the second half of gestation.</div></div><div><h3>Approach and results</h3><div>Using Cre-loxP lineage tracing with multiple reporters including the multifluorescent Confetti, we labelled TNAP+ precursors <em>in vivo</em> and assessed the smooth or skeletal muscle differentiation in their lineage at a perinatal stage. We found that TNAP+ cells contribute <em>in vivo</em> to skeletal and smooth muscle cells, as well as other pericytes, also during pre-natal muscle development. The resulting clones showed that such fate choices are likely to depend on distinct unipotent progenitors rather than multipotent progenitors. In addition, we isolated and differentiated <em>in vitro</em> foetal cells derived from TNAP+ precursors, which showed that they are not spontaneously myogenic unless co-cultured with other skeletal muscle cells.</div></div><div><h3>Conclusions</h3><div>This work extends our understanding of the differentiative potency of these non- canonical skeletal muscle progenitors during prenatal life, with a view to a future application of this knowledge to optimise cell therapies for muscle wasting disorders.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"159 ","pages":"Article 107489"},"PeriodicalIF":3.5,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-02DOI: 10.1016/j.vph.2025.107476
Lisa Alibrandi , Vincenzo Lionetti
Mitochondria are essential organelles that regulate cellular energy metabolism, redox balance, and signaling pathways related to proliferation, aging and survival. So far, significant interspecies differences exist in mitochondrial structure, function, and dynamics, which have critical implications for cardiovascular physiology and pharmacology. This review explores the main differences in mitochondrial properties across species of animals that are commonly used for translational research, emphasizing their cardiac and vascular relevance. By addressing key interspecies differences, including mitochondrial DNA (mtDNA) variation, bioenergetic profile, oxidative stress response, epigenetic regulation, mitochondrial biogenesis, and adaptive mechanisms, we aim to provide insights into the challenges and opportunities in translating preclinical findings to clinical applications. Understanding these interspecies differences is essential for optimizing the design and interpretation of preclinical studies and for developing effective mitochondrial-targeted therapies.
{"title":"Interspecies differences in mitochondria: Implications for cardiac and vascular translational research","authors":"Lisa Alibrandi , Vincenzo Lionetti","doi":"10.1016/j.vph.2025.107476","DOIUrl":"10.1016/j.vph.2025.107476","url":null,"abstract":"<div><div>Mitochondria are essential organelles that regulate cellular energy metabolism, redox balance, and signaling pathways related to proliferation, aging and survival. So far, significant interspecies differences exist in mitochondrial structure, function, and dynamics, which have critical implications for cardiovascular physiology and pharmacology. This review explores the main differences in mitochondrial properties across species of animals that are commonly used for translational research, emphasizing their cardiac and vascular relevance. By addressing key interspecies differences, including mitochondrial DNA (mtDNA) variation, bioenergetic profile, oxidative stress response, epigenetic regulation, mitochondrial biogenesis, and adaptive mechanisms, we aim to provide insights into the challenges and opportunities in translating preclinical findings to clinical applications. Understanding these interspecies differences is essential for optimizing the design and interpretation of preclinical studies and for developing effective mitochondrial-targeted therapies.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"159 ","pages":"Article 107476"},"PeriodicalIF":3.5,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-25DOI: 10.1016/j.vph.2025.107475
Thomas Mousso , Khanh Pham , Rhonda Drewes , Sefunmi Babatunde , Jessica Jong , Alanna Krug , Gabrielle Inserra , John Biber , Joseph A. Brazzo , Sachin Gupte , Yongho Bae
Aberrant changes in cell behaviors, such as proliferation, apoptosis, and migration, are some of the contributing factors to the development of various cardiovascular diseases (CVDs) and pathologies, including atherosclerosis, neointimal hyperplasia, and heart failure. In recent years, numerous studies have identified survivin, a key player in the anti-apoptotic pathway, to be extensively involved in modulating cellular functioning in cancer, with many reaching clinical trials. Though seemingly different, CVDs and cancer share abundant similarities regarding abnormal cell modifications and behaviors. This overlap has sparked growing interest in investigating survivin as a therapeutic target in the context of CVD. With new findings emerging rapidly, a comprehensive understanding of survivin's role in cardiovascular pathology is crucial to revealing its full therapeutic potential and translating these discoveries into effective treatments. This review discusses recent findings of survivin in CVDs and related pathologies, focusing on its dual role in promoting proliferation and inhibiting apoptosis, specifically in atherosclerosis, neointimal hyperplasia, stroke, hypertension, myocardial infarction, and heart failure. Across different cell types and pathological contexts, survivin plays a pivotal role throughout the disease progression–from the onset of disease development to the facilitation of compensatory mechanisms post-injury–primarily through its function in regulating cell proliferation and apoptosis. Furthermore, given the limited research on survivin as a therapeutic target for CVDs, potential clinical avenues, including YM155 (a survivin inhibitor) or adenoviral, adeno-associated, and lentiviral vectors, are also discussed. Overall, this review highlights survivin as a promising target for mitigating the detrimental effects of CVDs and to provide new perspectives to advance research on the intervention of CVDs and associated pathologies.
{"title":"Survivin in cardiovascular diseases and its therapeutic potential","authors":"Thomas Mousso , Khanh Pham , Rhonda Drewes , Sefunmi Babatunde , Jessica Jong , Alanna Krug , Gabrielle Inserra , John Biber , Joseph A. Brazzo , Sachin Gupte , Yongho Bae","doi":"10.1016/j.vph.2025.107475","DOIUrl":"10.1016/j.vph.2025.107475","url":null,"abstract":"<div><div>Aberrant changes in cell behaviors, such as proliferation, apoptosis, and migration, are some of the contributing factors to the development of various cardiovascular diseases (CVDs) and pathologies, including atherosclerosis, neointimal hyperplasia, and heart failure. In recent years, numerous studies have identified survivin, a key player in the anti-apoptotic pathway, to be extensively involved in modulating cellular functioning in cancer, with many reaching clinical trials. Though seemingly different, CVDs and cancer share abundant similarities regarding abnormal cell modifications and behaviors. This overlap has sparked growing interest in investigating survivin as a therapeutic target in the context of CVD. With new findings emerging rapidly, a comprehensive understanding of survivin's role in cardiovascular pathology is crucial to revealing its full therapeutic potential and translating these discoveries into effective treatments. This review discusses recent findings of survivin in CVDs and related pathologies, focusing on its dual role in promoting proliferation and inhibiting apoptosis, specifically in atherosclerosis, neointimal hyperplasia, stroke, hypertension, myocardial infarction, and heart failure. Across different cell types and pathological contexts, survivin plays a pivotal role throughout the disease progression–from the onset of disease development to the facilitation of compensatory mechanisms post-injury–primarily through its function in regulating cell proliferation and apoptosis. Furthermore, given the limited research on survivin as a therapeutic target for CVDs, potential clinical avenues, including YM155 (a survivin inhibitor) or adenoviral, adeno-associated, and lentiviral vectors, are also discussed. Overall, this review highlights survivin as a promising target for mitigating the detrimental effects of CVDs and to provide new perspectives to advance research on the intervention of CVDs and associated pathologies.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"159 ","pages":"Article 107475"},"PeriodicalIF":3.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143508341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In recent years, the therapeutic utility of mesenchymal stem cells (MSCs) has received substantial attention from investigators, owing to their pleiotropic properties. The emerging insights from the developments in tissue engineering provide perspectives for the repair of damaged tissue and the replacement of failing organs. Perivascular cells including MSC-like pericytes, vascular smooth muscles, and other cells located around blood vessels, have been acknowledged to contribute to in situ angiogenesis and repair process. MSCs offer a wide array of therapeutic applications in different pathological states. However, in the current article, we have highlighted the recent updates on MSCs and their key applications in cardiac and cerebrovascular diseases, evident in different preclinical and clinical studies. We believe the present article would assist the investigators in understanding the recent advances of MSCs and exploring their therapeutic potential in varied ailments, especially cardiac and cerebrovascular diseases.
{"title":"Emerging role of mesenchymal cells in cardiac and cerebrovascular diseases: Physiology, pathology, and therapeutic implications","authors":"Kajal Kumari , Kanika Verma , Meenal Sahu , Jaya Dwivedi , Sarvesh Paliwal , Swapnil Sharma","doi":"10.1016/j.vph.2025.107473","DOIUrl":"10.1016/j.vph.2025.107473","url":null,"abstract":"<div><div>In recent years, the therapeutic utility of mesenchymal stem cells (MSCs) has received substantial attention from investigators, owing to their pleiotropic properties. The emerging insights from the developments in tissue engineering provide perspectives for the repair of damaged tissue and the replacement of failing organs. Perivascular cells including MSC-like pericytes, vascular smooth muscles, and other cells located around blood vessels, have been acknowledged to contribute to in situ angiogenesis and repair process. MSCs offer a wide array of therapeutic applications in different pathological states. However, in the current article, we have highlighted the recent updates on MSCs and their key applications in cardiac and cerebrovascular diseases, evident in different preclinical and clinical studies. We believe the present article would assist the investigators in understanding the recent advances of MSCs and exploring their therapeutic potential in varied ailments, especially cardiac and cerebrovascular diseases.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"159 ","pages":"Article 107473"},"PeriodicalIF":3.5,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Glycosylation is a post-translational modification in which complex, branched carbohydrates (glycans) are covalently attached to proteins or lipids. Asparagine-link protein (N-) glycosylation is among the most common types of glycosylation. This process is essential for many biological and cellular functions, and impaired N-glycosylation has been widely implicated in inflammation and cardiovascular diseases. Different technical approaches have been used to increase the coverage of the N-glycome, revealing a high level of complexity of glycans, regarding their structure and attachment site on a protein. In this context, new insights from genomic studies have revealed a genetic regulation of glycosylation, linking genetic variants to total plasma N-glycosylation and N-glycosylation of immunoglobulin G (IgG). In addition, RNAseq approaches have revealed a degree of transcriptional regulation for the glycoenzymes involved in glycan structure. However, our understanding of the association between cardiovascular risk and glycosylation, determined by a complex overlay of genetic and environmental factors, remains limited. Mostly, plasma N-glycosylation profiling in different human cohorts or experimental investigations of specific enzyme functions in models of atherosclerosis have been reported. Most of the uncovered glycosylation associations with pathological mechanisms revolve around the recruitment of inflammatory cells to the vessel wall and lipoprotein metabolism. This review aims to summarise insights from omics studies into the immune and metabolic regulation of N-glycosylation and its association with cardiovascular and metabolic disease risk and to provide mechanistic insights from experimental models.
The combination of emerging techniques for glycomics and glycoproteomics with already achieved omics approaches to map the transcriptomic, epigenomic, and metabolomic profile at single-cell resolution will deepen our understanding of the molecular regulation of glycosylation as well as identify novel biomarkers and targets for cardiovascular disease prevention and treatment.
{"title":"N-glycosylation signature and its relevance in cardiovascular immunometabolism","authors":"Monika Svecla , Ruifang Li-Gao , David Falck , Fabrizia Bonacina","doi":"10.1016/j.vph.2025.107474","DOIUrl":"10.1016/j.vph.2025.107474","url":null,"abstract":"<div><div>Glycosylation is a post-translational modification in which complex, branched carbohydrates (glycans) are covalently attached to proteins or lipids. Asparagine-link protein (<em>N</em>-) glycosylation is among the most common types of glycosylation. This process is essential for many biological and cellular functions, and impaired <em>N</em>-glycosylation has been widely implicated in inflammation and cardiovascular diseases. Different technical approaches have been used to increase the coverage of the <em>N</em>-glycome, revealing a high level of complexity of glycans, regarding their structure and attachment site on a protein. In this context, new insights from genomic studies have revealed a genetic regulation of glycosylation, linking genetic variants to total plasma <em>N</em>-glycosylation and <em>N</em>-glycosylation of immunoglobulin G (IgG). In addition, RNAseq approaches have revealed a degree of transcriptional regulation for the glycoenzymes involved in glycan structure. However, our understanding of the association between cardiovascular risk and glycosylation, determined by a complex overlay of genetic and environmental factors, remains limited. Mostly, plasma <em>N</em>-glycosylation profiling in different human cohorts or experimental investigations of specific enzyme functions in models of atherosclerosis have been reported. Most of the uncovered glycosylation associations with pathological mechanisms revolve around the recruitment of inflammatory cells to the vessel wall and lipoprotein metabolism. This review aims to summarise insights from omics studies into the immune and metabolic regulation of <em>N</em>-glycosylation and its association with cardiovascular and metabolic disease risk and to provide mechanistic insights from experimental models.</div><div>The combination of emerging techniques for glycomics and glycoproteomics with already achieved omics approaches to map the transcriptomic, epigenomic, and metabolomic profile at single-cell resolution will deepen our understanding of the molecular regulation of glycosylation as well as identify novel biomarkers and targets for cardiovascular disease prevention and treatment.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"159 ","pages":"Article 107474"},"PeriodicalIF":3.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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