ArticleCardiovascular research2019
TRPV4 increases cardiomyocyte calcium cycling and contractility yet contributes to damage in the aged heart following hypoosmotic stress.
Article in Cardiovascular research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 80 citations in OpenAlex.
- Cardiac mechanotransduction from development to disease.APL bioengineering · 2026Review
- Mitochondrial Adaptation to Mechanical Stress in Cardiac Ageing and Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- TRPV4-Mediated Mechanosensing Regulates the Endothelial-to-Mesenchymal Transition: Implications for Atherosclerosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Regulation of Collecting Lymphatic Vessel Contractile Function by TRPV4 Channels.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Transient receptor potential vanilloid type 4 channels mediate bladder cancer cell proliferation, migration, and chemoresistance.The Journal of pharmacology and experimental therapeutics · 2025Article
- Effects of High Glucose on Simulated Ischemia/Reperfusion Injury in Isolated Cardiomyocytes.International journal of molecular sciences · 2025Article
- TRPV4 activation by TGFβ2 enhances cellular contractility and drives ocular hypertension.eLife · 2025Article
- Trpv4-mediated mechanotransduction regulates the differentiation of valvular interstitial cells to myofibroblasts: implications for aortic valve stenosis.American journal of physiology. Cell physiology · 2025Article
- Taxing Hearts:Circulation research · 2025Article
- Article
- Unlocking the potential of cardiac TRP channels using knockout mice models.Frontiers in physiology · 2025Article
- Low-Intensity Extracorporeal Shock Wave Therapy Ameliorates Detrusor Hyperactivity with Impaired Contractility via Transient Potential Vanilloid Channels: A Rat Model for Ovarian Hormone Deficiency.International journal of molecular sciences · 2024Article
- Cardiovascular perspectives of the TRP channel polycystin 2.The Journal of physiology · 2024Article
- Mechanosensitive TRPV4 channel guides maturation and organization of the bilayered mammary epithelium.Scientific reports · 2024Article
- TRPV4 Channels Promote Pathological, but Not Physiological, Cardiac Remodeling through the Activation of Calcineurin/NFAT and TRPC6.International journal of molecular sciences · 2024Article
- The Multifaceted Functions of TRPV4 and Calcium Oscillations in Tissue Repair.International journal of molecular sciences · 2024Review
- Nongenetic Optical Modulation of Pluripotent Stem Cells Derived Cardiomyocytes Function in the Red Spectral Range.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Deletion of Endothelial TRPV4 Protects Heart From Pressure Overload-Induced Hypertrophy.Hypertension (Dallas, Tex. : 1979) · 2023Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Aims: Cardiomyocyte Ca2+ homeostasis is altered with aging via poorly-understood mechanisms. The Transient Receptor Potential Vanilloid 4 (TRPV4) ion channel is an osmotically-activated Ca2+ channel, and there is limited information on the role of TRPV4 in cardiomyocytes. Our data show that TRPV4 protein expression increases in cardiomyocytes of the aged heart. The objective of this study was to examine the role of TRPV4 in cardiomyocyte Ca2+ homeostasis following hypoosmotic stress and to assess the contribution of TRPV4 to cardiac contractility and tissue damage following ischaemia-reperfusion (I/R), a pathological condition associated with cardiomyocyte osmotic stress. Methods and results: TRPV4 protein expression increased in cardiomyocytes of Aged (24-27 months) mice compared with Young (3-6 months) mice. Immunohistochemistry revealed TRPV4 localization to microtubules and the t-tubule network of cardiomyocytes of Aged mice, as well as in left ventricular myocardium of elderly patients undergoing surgical aortic valve replacement for aortic stenosis. Following hypoosmotic stress, cardiomyocytes of Aged, but not Young exhibited an increase in action-potential induced Ca2+ transients. This effect was mediated via increased sarcoplasmic reticulum Ca2+ content and facilitation of Ryanodine Receptor Ca2+ release and was prevented by TRPV4 antagonism (1 μmol/L HC067047). A similar hypoosmotic stress-induced facilitation of Ca2+ transients was observed in Young transgenic mice with inducible TRPV4 expression in cardiomyocytes. Following I/R, isolated hearts of Young mice with transgenic TRPV4 expression exhibited enhanced contractility vs. hearts of Young control mice. Similarly, hearts of Aged mice exhibited enhanced contractility vs. hearts of Aged TRPV4 knock-out (TRPV4-/-) mice. In Aged, pharmacological inhibition of TRPV4 (1 μmol/L, HC067047) prevented hypoosmotic stress-induced cardiomyocyte death and I/R-induced cardiac damage. Conclusions: Our findings provide a new mechanism for hypoosmotic stress-induced cardiomyocyte Ca2+ entry and cell damage in the aged heart. These finding have potential implications in treatment of elderly populations at increased risk of myocardial infarction and I/R injury.
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