Pub Date : 2024-05-03DOI: 10.1152/ajpheart.00211.2024
Felix Braczko, Sara Romina Fischl, Jörg Reinders, Helmut Raphael Lieder, Petra Kleinbongard
Background: Activation of the vagus nerve mediates cardioprotection and attenuates myocardial ischemia/reperfusion (I/R) injury. In response to vagal activation, acetylcholine (ACh) is released from the intracardiac nervous system (ICNS) and activates intracellular cardioprotective signaling cascades. Recently, however, a non-neuronal cholinergic cardiac system (NNCCS) in cardiomyocytes has been described as an additional source of ACh. Aim: To investigate whether the NNCCS mediates cardioprotection in absence of vagal and ICNS activation. For that, we used a reductionist approach of isolated adult rat ventricular cardiomyocytes in absence of neuronal cells with hypoxic preconditioning (HPC) as protective stimulus. Methods: Adult rat ventricular cardiomyocytes were isolated, absence of neuronal cells was confirmed, HPC was induced by 10/20 min hypoxia/reoxygenation (H/R) before subjection to 30/5 min H/R to simulate I/R injury. Cardiomyocyte viability was assessed by trypan blue staining. Intra- and extracellular ACh was quantified using liquid chromatography-coupled mass spectrometry at baseline, after HPC, after hypoxia, and after reoxygenation, respectively. In a subset of experiments, muscarinic/nicotinic ACh receptor (mAChR/nAChR) antagonists were added during HPC or during H/R. Results: Cardiomyocyte viability at baseline (69±4%) was reduced by H/R (10±3%). With HPC cardiomyocyte viability was preserved after H/R (25±6%). Intra- and extracellular ACh increased during hypoxia, HPC further increased both intra- and extracellular ACh (from 0.9±0.7 to 1.5±1.0 nmol/mg; from 0.7±0.6 to 1.1±0.7 nmol/mg). Addition of mAChR and nAChR antagonists during HPC had no impact on HPC´s protection, however protection was abrogated when antagonists were added during H/R (cardiomyocyte viability after H/R: 23±5%; 13±4%). Conclusion: Activation of the NNCCS is involved in cardiomyocyte protection: HPC increases intra- and extracellular ACh during H/R, and m-/nAChRs are causally involved in HPC´s cardiomyocyte protection during H/R. The interplay between upstream ICNS activation and the NNCCS activation to myocardial cholinergic metabolism and cardioprotection needs to be investigated in future studies.
{"title":"Activation of the non-neuronal cholinergic cardiac system by hypoxic preconditioning protects isolated adult cardiomyocytes from hypoxia/reoxygenation injury","authors":"Felix Braczko, Sara Romina Fischl, Jörg Reinders, Helmut Raphael Lieder, Petra Kleinbongard","doi":"10.1152/ajpheart.00211.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00211.2024","url":null,"abstract":"Background: Activation of the vagus nerve mediates cardioprotection and attenuates myocardial ischemia/reperfusion (I/R) injury. In response to vagal activation, acetylcholine (ACh) is released from the intracardiac nervous system (ICNS) and activates intracellular cardioprotective signaling cascades. Recently, however, a non-neuronal cholinergic cardiac system (NNCCS) in cardiomyocytes has been described as an additional source of ACh. Aim: To investigate whether the NNCCS mediates cardioprotection in absence of vagal and ICNS activation. For that, we used a reductionist approach of isolated adult rat ventricular cardiomyocytes in absence of neuronal cells with hypoxic preconditioning (HPC) as protective stimulus. Methods: Adult rat ventricular cardiomyocytes were isolated, absence of neuronal cells was confirmed, HPC was induced by 10/20 min hypoxia/reoxygenation (H/R) before subjection to 30/5 min H/R to simulate I/R injury. Cardiomyocyte viability was assessed by trypan blue staining. Intra- and extracellular ACh was quantified using liquid chromatography-coupled mass spectrometry at baseline, after HPC, after hypoxia, and after reoxygenation, respectively. In a subset of experiments, muscarinic/nicotinic ACh receptor (mAChR/nAChR) antagonists were added during HPC or during H/R. Results: Cardiomyocyte viability at baseline (69±4%) was reduced by H/R (10±3%). With HPC cardiomyocyte viability was preserved after H/R (25±6%). Intra- and extracellular ACh increased during hypoxia, HPC further increased both intra- and extracellular ACh (from 0.9±0.7 to 1.5±1.0 nmol/mg; from 0.7±0.6 to 1.1±0.7 nmol/mg). Addition of mAChR and nAChR antagonists during HPC had no impact on HPC´s protection, however protection was abrogated when antagonists were added during H/R (cardiomyocyte viability after H/R: 23±5%; 13±4%). Conclusion: Activation of the NNCCS is involved in cardiomyocyte protection: HPC increases intra- and extracellular ACh during H/R, and m-/nAChRs are causally involved in HPC´s cardiomyocyte protection during H/R. The interplay between upstream ICNS activation and the NNCCS activation to myocardial cholinergic metabolism and cardioprotection needs to be investigated in future studies.","PeriodicalId":7640,"journal":{"name":"American Journal of Physiology - Heart and Circulatory Physiology","volume":"85 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140831193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-03DOI: 10.1152/ajpheart.00043.2024
Karthikeyan Bose, Herbert M. Espinoza, Samantha Louey, Sonnet S. Jonker
American Journal of Physiology-Heart and Circulatory Physiology, Ahead of Print.
美国生理学杂志-心脏与循环生理学》，提前出版。
{"title":"Sensitivity and activation of endoplasmic reticulum stress response and apoptosis in the perinatal sheep heart","authors":"Karthikeyan Bose, Herbert M. Espinoza, Samantha Louey, Sonnet S. Jonker","doi":"10.1152/ajpheart.00043.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00043.2024","url":null,"abstract":"American Journal of Physiology-Heart and Circulatory Physiology, Ahead of Print. <br/>","PeriodicalId":7640,"journal":{"name":"American Journal of Physiology - Heart and Circulatory Physiology","volume":"279 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140830963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-03DOI: 10.1152/ajpheart.00746.2023
Markus Neuhäuser, Graeme D. Ruxton
American Journal of Physiology-Heart and Circulatory Physiology, Ahead of Print.
美国生理学杂志-心脏与循环生理学》，提前出版。
{"title":"Perspective on statistical power and equivalences tests","authors":"Markus Neuhäuser, Graeme D. Ruxton","doi":"10.1152/ajpheart.00746.2023","DOIUrl":"https://doi.org/10.1152/ajpheart.00746.2023","url":null,"abstract":"American Journal of Physiology-Heart and Circulatory Physiology, Ahead of Print. <br/>","PeriodicalId":7640,"journal":{"name":"American Journal of Physiology - Heart and Circulatory Physiology","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140830964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-03DOI: 10.1152/ajpheart.00020.2024
Danielle E. Berbrier, Tessa E. Adler, Cheryl A. Leone, Michael J. Paidas, Nina S. Stachenfeld, Charlotte W. Usselman
Preeclampsia is a risk factor for future cardiovascular diseases. However, the mechanisms underlying this association remain unclear, limiting effective prevention strategies. Blood pressure responses to acute stimuli may reveal cardiovascular dysfunction not apparent at rest, identifying individuals at elevated cardiovascular risk. Therefore, we compared blood pressure responsiveness to acute stimuli between previously preeclamptic (PPE) women (34±5yr, 13±6 months postpartum) and women following healthy pregnancies (CTRL; 29±3yr, 15±4 months postpartum). Blood pressure (finger photoplethysmography calibrated to manual sphygmomanometry-derived values; PPE: n=12, CTRL: n=12) was assessed during end-expiratory apnea, mental stress, and isometric handgrip exercise protocols. Integrated muscle sympathetic nerve activity (MSNA) was assessed in a subset of participants (peroneal nerve microneurography; PPE: n=6, CTRL: n=8). Across all protocols, systolic blood pressure (SBP) was higher in PPE than CTRL (main effects of group all P<0.05). Peak changes in SBP were stressor-specific: peak increases in SBP were not different between PPE and CTRL during apnea (+8±6 vs. +6±5mmHg, P=0.32) or mental stress (+9±5 vs. +4±7mmHg, P=0.06). However, peak exercise-induced increases in SBP were greater in PPE than CTRL (+11±5 vs. +7±7mmHg, P=0.04). MSNA was higher in PPE than CTRL across all protocols (main effects of group all P<0.05), and increases in peak MSNA were greater in PPE than CTRL during apnea (+44±6 vs. +27±14burst/100hb, P=0.04) and exercise (+25±8 vs. +13±11burst/100hb, P=0.01) but not different between groups during mental stress (+2±3 vs. 0±5burst/100hb, P=0.41). Exaggerated pressor and sympathetic responses to certain stimuli may contribute to the elevated long-term risk for cardiovascular disease in PPE.
先兆子痫是未来心血管疾病的一个风险因素。然而，这种关联的机制仍不清楚，从而限制了有效的预防策略。血压对急性刺激的反应可揭示静息状态下不明显的心血管功能障碍，从而识别心血管风险升高的个体。因此，我们比较了曾患有先兆子痫（PPE）的妇女（34±5 岁，产后 13±6 个月）和健康妊娠妇女（CTRL；29±3 岁，产后 15±4 个月）对急性刺激的血压反应。在呼气末呼吸暂停、精神紧张和等长手握运动方案期间，对血压（根据手动血压计得出的值校准的手指血压计；PPE：12 人，CTRL：12 人）进行了评估。对一部分参与者的综合肌肉交感神经活动（MSNA）进行了评估（腓肠神经微神经电图；PPE：n=6，CTRL：n=8）。在所有方案中，PPE 的收缩压 (SBP) 均高于 CTRL（组别的主效应均为 P<0.05）。SBP 的峰值变化具有应激特异性：在呼吸暂停（+8±6 vs. +6±5mmHg，P=0.32）或精神压力（+9±5 vs. +4±7mmHg，P=0.06）时，PPE 和 CTRL 的 SBP 峰值增加没有差异。然而，PPE 运动引起的 SBP 峰值升高比 CTRL 更大（+11±5 vs. +7±7mmHg，P=0.04）。在所有方案中，PPE 的 MSNA 均高于 CTRL（各组的主效应均为 P<0.05），在呼吸暂停（+44±6 vs. +27±14burst/100hb, P=0.04）和运动（+25±8 vs. +13±11burst/100hb, P=0.01）时，PPE 的 MSNA 峰值增加高于 CTRL，但在精神压力时，各组间无差异（+2±3 vs. 0±5burst/100hb, P=0.41）。对某些刺激的过度加压和交感反应可能是 PPE 长期罹患心血管疾病风险升高的原因。
{"title":"Blood pressure responses to handgrip exercise but not apnea or mental stress are enhanced in women with a recent history of preeclampsia","authors":"Danielle E. Berbrier, Tessa E. Adler, Cheryl A. Leone, Michael J. Paidas, Nina S. Stachenfeld, Charlotte W. Usselman","doi":"10.1152/ajpheart.00020.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00020.2024","url":null,"abstract":"Preeclampsia is a risk factor for future cardiovascular diseases. However, the mechanisms underlying this association remain unclear, limiting effective prevention strategies. Blood pressure responses to acute stimuli may reveal cardiovascular dysfunction not apparent at rest, identifying individuals at elevated cardiovascular risk. Therefore, we compared blood pressure responsiveness to acute stimuli between previously preeclamptic (PPE) women (34±5yr, 13±6 months postpartum) and women following healthy pregnancies (CTRL; 29±3yr, 15±4 months postpartum). Blood pressure (finger photoplethysmography calibrated to manual sphygmomanometry-derived values; PPE: n=12, CTRL: n=12) was assessed during end-expiratory apnea, mental stress, and isometric handgrip exercise protocols. Integrated muscle sympathetic nerve activity (MSNA) was assessed in a subset of participants (peroneal nerve microneurography; PPE: n=6, CTRL: n=8). Across all protocols, systolic blood pressure (SBP) was higher in PPE than CTRL (main effects of group all <i>P<0.05</i>). Peak changes in SBP were stressor-specific: peak increases in SBP were not different between PPE and CTRL during apnea (+8±6 <i>vs.</i> +6±5mmHg, <i>P=0.32</i>) or mental stress (+9±5 <i>vs.</i> +4±7mmHg, <i>P=0.06</i>). However, peak exercise-induced increases in SBP were greater in PPE than CTRL (+11±5 <i>vs.</i> +7±7mmHg, <i>P=0.04</i>). MSNA was higher in PPE than CTRL across all protocols (main effects of group all <i>P<0.05</i>), and increases in peak MSNA were greater in PPE than CTRL during apnea (+44±6 <i>vs.</i> +27±14burst/100hb, <i>P=0.04</i>) and exercise (+25±8 <i>vs.</i> +13±11burst/100hb, <i>P=0.01</i>) but not different between groups during mental stress (+2±3 <i>vs.</i> 0±5burst/100hb, <i>P=0.41</i>). Exaggerated pressor and sympathetic responses to certain stimuli may contribute to the elevated long-term risk for cardiovascular disease in PPE.","PeriodicalId":7640,"journal":{"name":"American Journal of Physiology - Heart and Circulatory Physiology","volume":"279 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140830909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-03DOI: 10.1152/ajpheart.00225.2024
Mami Hamaoka, Urs A. Leuenberger, Zhaohui Gao, Faisal Aziz, Danielle Jin-Kwang Kim, Jonathan Carter Luck, Cheryl Blaha, Aimee E. Cauffman, Lawrence I. Sinoway, Jian Cui
American Journal of Physiology-Heart and Circulatory Physiology, Ahead of Print.
美国生理学杂志-心脏与循环生理学》，提前出版。
{"title":"Effects of Acute Hyperoxia on Autonomic Function and Coronary Tone in Patients with Peripheral Artery Disease","authors":"Mami Hamaoka, Urs A. Leuenberger, Zhaohui Gao, Faisal Aziz, Danielle Jin-Kwang Kim, Jonathan Carter Luck, Cheryl Blaha, Aimee E. Cauffman, Lawrence I. Sinoway, Jian Cui","doi":"10.1152/ajpheart.00225.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00225.2024","url":null,"abstract":"American Journal of Physiology-Heart and Circulatory Physiology, Ahead of Print. <br/>","PeriodicalId":7640,"journal":{"name":"American Journal of Physiology - Heart and Circulatory Physiology","volume":"63 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140831104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-03DOI: 10.1152/ajpheart.00133.2024
Michael G Leahy, Stephen A. Busch, Scott F. Thrall, Sam J. Hillen, A. William Sheel, Glen E. Foster
American Journal of Physiology-Heart and Circulatory Physiology, Ahead of Print.
美国生理学杂志-心脏与循环生理学》，提前出版。
{"title":"Reflex sympathetic activation to inspiratory muscle loading is attenuated in females relative to males","authors":"Michael G Leahy, Stephen A. Busch, Scott F. Thrall, Sam J. Hillen, A. William Sheel, Glen E. Foster","doi":"10.1152/ajpheart.00133.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00133.2024","url":null,"abstract":"American Journal of Physiology-Heart and Circulatory Physiology, Ahead of Print. <br/>","PeriodicalId":7640,"journal":{"name":"American Journal of Physiology - Heart and Circulatory Physiology","volume":"117 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140830912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-19DOI: 10.1152/ajpheart.00325.2023
Emanuele Pizzo, Daniel O. Cervantes, Harshada Ketkar, Valentina Ripa, Drew M. Nassal, Benjamin Buck, Sreema P. Parambath, Valeria Di Stefano, Kanwardeep Singh, Carl I. Thompson, Peter J. Mohler, Thomas J. Hund, Jason T. Jacobson, Sudhir Jain, Marcello Rota
Diastolic dysfunction and delayed ventricular repolarization are typically observed in the elderly, but whether these defects are intimately associated in the progressive manifestation of the aging myopathy remains to be determined. In this regard, aging in experimental animals is coupled with increased late Na+ current (INaL) in cardiomyocytes, raising the possibility that INaL conditions the modality of electrical recovery and myocardial relaxation of the aged heart. For this purpose, aging male and female wild-type (WT) C57Bl/6 mice were studied together with genetically engineered mice with phosphomimetic (gain-of-function, GoF) or ablated (loss-of-function, LoF) mutations of the sodium channel Nav1.5 at Ser571 associated with, respectively, increased and stabilized INaL. At ~18 months (m) of age, WT mice developed prolonged duration of the QT interval of the electrocardiogram and impaired diastolic left ventricular (LV) filling, defects that were reversed by INaL inhibition. Prolonged repolarization and impaired LV filling occurred prematurely in adult (~5 m) GoF mutant mice, whereas these alterations were largely attenuated in aging LoF mutant animals. Ca2+ transient decay and kinetics of myocyte shortening/relengthening were delayed in aged (~24 m) WT myocytes, with respect to adult cells. In contrast, delayed Ca2+ transients and contractile dynamics occurred at adult stage in GoF myocytes and further deteriorated at old age. Conversely, myocyte mechanics were minimally affected in aging LoF cells. Collectively, these results document that Nav1.5 phosphorylation at Ser571 and the late Na+ current modulates the modality of myocyte relaxation, constituting the mechanism linking delayed ventricular repolarization and diastolic dysfunction.
{"title":"Phosphorylation of Cardiac Sodium Channel at Ser571 Anticipates Manifestations of the Aging Myopathy","authors":"Emanuele Pizzo, Daniel O. Cervantes, Harshada Ketkar, Valentina Ripa, Drew M. Nassal, Benjamin Buck, Sreema P. Parambath, Valeria Di Stefano, Kanwardeep Singh, Carl I. Thompson, Peter J. Mohler, Thomas J. Hund, Jason T. Jacobson, Sudhir Jain, Marcello Rota","doi":"10.1152/ajpheart.00325.2023","DOIUrl":"https://doi.org/10.1152/ajpheart.00325.2023","url":null,"abstract":"Diastolic dysfunction and delayed ventricular repolarization are typically observed in the elderly, but whether these defects are intimately associated in the progressive manifestation of the aging myopathy remains to be determined. In this regard, aging in experimental animals is coupled with increased late Na<sup>+</sup> current (I<sub>NaL</sub>) in cardiomyocytes, raising the possibility that I<sub>NaL</sub> conditions the modality of electrical recovery and myocardial relaxation of the aged heart. For this purpose, aging male and female wild-type (WT) C57Bl/6 mice were studied together with genetically engineered mice with phosphomimetic (gain-of-function, GoF) or ablated (loss-of-function, LoF) mutations of the sodium channel Nav1.5 at Ser571 associated with, respectively, increased and stabilized I<sub>NaL</sub>. At ~18 months (m) of age, WT mice developed prolonged duration of the QT interval of the electrocardiogram and impaired diastolic left ventricular (LV) filling, defects that were reversed by I<sub>NaL</sub> inhibition. Prolonged repolarization and impaired LV filling occurred prematurely in adult (~5 m) GoF mutant mice, whereas these alterations were largely attenuated in aging LoF mutant animals. Ca<sup>2+</sup> transient decay and kinetics of myocyte shortening/relengthening were delayed in aged (~24 m) WT myocytes, with respect to adult cells. In contrast, delayed Ca<sup>2+</sup> transients and contractile dynamics occurred at adult stage in GoF myocytes and further deteriorated at old age. Conversely, myocyte mechanics were minimally affected in aging LoF cells. Collectively, these results document that Nav1.5 phosphorylation at Ser571 and the late Na<sup>+</sup> current modulates the modality of myocyte relaxation, constituting the mechanism linking delayed ventricular repolarization and diastolic dysfunction.","PeriodicalId":7640,"journal":{"name":"American Journal of Physiology - Heart and Circulatory Physiology","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140627309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-19DOI: 10.1152/ajpheart.00068.2024
Vaishnavi Aradhyula, Rohit Vyas, Prabhatchandra Dube, Steven T. Haller, Rajesh Gupta, Krishna Rao Maddipati, David J. Kennedy, Samer J. Khouri
American Journal of Physiology-Heart and Circulatory Physiology, Ahead of Print.
美国生理学杂志-心脏与循环生理学》，提前出版。
{"title":"Novel Insights into the Pathobiology of Pulmonary Hypertension in Heart Failure with Preserved Ejection Fraction","authors":"Vaishnavi Aradhyula, Rohit Vyas, Prabhatchandra Dube, Steven T. Haller, Rajesh Gupta, Krishna Rao Maddipati, David J. Kennedy, Samer J. Khouri","doi":"10.1152/ajpheart.00068.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00068.2024","url":null,"abstract":"American Journal of Physiology-Heart and Circulatory Physiology, Ahead of Print. <br/>","PeriodicalId":7640,"journal":{"name":"American Journal of Physiology - Heart and Circulatory Physiology","volume":"98 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140627476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-19DOI: 10.1152/ajpheart.00795.2023
Leslie M. Ogilvie, Bridget Coyle-Asbil, Keith R. Brunt, Jim Petrik, Jeremy A. Simpson
Cardiovascular disease (CVD) and cancer are the leading causes of mortality worldwide. Although generally thought of as distinct diseases, the intersectional overlap between CVD and cancer is increasingly evident in both causal and mechanistic relationships. The field of cardio-oncology is largely focused on cardiotoxic effects of cancer therapies (e.g., chemotherapy, radiation). Further, the cumulative effects of cardiotoxic therapy exposure and the prevalence of CVD risk factors in cancer patients leads to long-term morbidity and poor quality of life in this patient population-even when patients are cancer-free. Evidence from cancer patients and animal models demonstrates that the presence of malignancy itself, independent of cardiotoxic therapy exposure or CVD risk factors, negatively impacts cardiac structure and function. As such, the primary focus of this review is the cardiac pathophysiologic and molecular features of therapy-naïve cancer. We also summarize the strengths and limitations of preclinical cancer models for cardio-oncology research and discuss therapeutic strategies that have been tested experimentally for the treatment of cancer-induced cardiac atrophy and dysfunction. Finally, we explore an adjacent area of interest, called 'reverse cardio-oncology', where the sequelae of heart failure augment cancer progression. Here, we emphasize the cross-disease communication between malignancy and the injured heart, and discuss the importance of chronic low-grade inflammation and endocrine factors in the progression of both diseases.
{"title":"Therapy-naïve malignancy causes cardiovascular disease: A state-of-the-art cardio-oncology perspective","authors":"Leslie M. Ogilvie, Bridget Coyle-Asbil, Keith R. Brunt, Jim Petrik, Jeremy A. Simpson","doi":"10.1152/ajpheart.00795.2023","DOIUrl":"https://doi.org/10.1152/ajpheart.00795.2023","url":null,"abstract":"Cardiovascular disease (CVD) and cancer are the leading causes of mortality worldwide. Although generally thought of as distinct diseases, the intersectional overlap between CVD and cancer is increasingly evident in both causal and mechanistic relationships. The field of cardio-oncology is largely focused on cardiotoxic effects of cancer therapies (e.g., chemotherapy, radiation). Further, the cumulative effects of cardiotoxic therapy exposure and the prevalence of CVD risk factors in cancer patients leads to long-term morbidity and poor quality of life in this patient population-even when patients are cancer-free. Evidence from cancer patients and animal models demonstrates that the presence of malignancy itself, independent of cardiotoxic therapy exposure or CVD risk factors, negatively impacts cardiac structure and function. As such, the primary focus of this review is the cardiac pathophysiologic and molecular features of therapy-naïve cancer. We also summarize the strengths and limitations of preclinical cancer models for cardio-oncology research and discuss therapeutic strategies that have been tested experimentally for the treatment of cancer-induced cardiac atrophy and dysfunction. Finally, we explore an adjacent area of interest, called 'reverse cardio-oncology', where the sequelae of heart failure augment cancer progression. Here, we emphasize the cross-disease communication between malignancy and the injured heart, and discuss the importance of chronic low-grade inflammation and endocrine factors in the progression of both diseases.","PeriodicalId":7640,"journal":{"name":"American Journal of Physiology - Heart and Circulatory Physiology","volume":"103 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140627304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：