Piezo2 is not an indispensable mechanosensor in murine cardiomyocytes
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Piezo2 is not an indispensable mechanosensor in murine cardiomyocytes. / Kloth, Benjamin; Mearini, Giulia; Weinberger, Florian; Stenzig, Justus; Geertz, Birgit; Starbatty, Jutta; Lindner, Diana; Schumacher, Udo; Reichenspurner, Hermann; Eschenhagen, Thomas; Hirt, Marc N.
In: SCI REP-UK, Vol. 12, No. 1, 8193, 17.05.2022.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Piezo2 is not an indispensable mechanosensor in murine cardiomyocytes
AU - Kloth, Benjamin
AU - Mearini, Giulia
AU - Weinberger, Florian
AU - Stenzig, Justus
AU - Geertz, Birgit
AU - Starbatty, Jutta
AU - Lindner, Diana
AU - Schumacher, Udo
AU - Reichenspurner, Hermann
AU - Eschenhagen, Thomas
AU - Hirt, Marc N
N1 - © 2022. The Author(s).
PY - 2022/5/17
Y1 - 2022/5/17
N2 - A short-term increase in ventricular filling leads to an immediate (Frank-Starling mechanism) and a slower (Anrep effect) rise in cardiac contractility, while long-term increased cardiac load (e.g., in arterial hypertension) decreases contractility. Whether these answers to mechanical tension are mediated by specific sensors in cardiomyocytes remains elusive. In this study, the piezo2 protein was evaluated as a potential mechanosensor. Piezo2 was found to be upregulated in various rat and mouse cardiac tissues upon mechanical or pharmacological stress. To investigate its function, C57BL/6J mice with homozygous cardiomyocyte-specific piezo2 knockout [Piezo2-KO] were created. To this end, α-MHC-Cre mice were crossed with homozygous "floxed" piezo2 mice. α-MHC-Cre mice crossed with wildtype mice served as controls [WT-Cre+]. In cardiomyocytes of Piezo2-KO mice, piezo2 mRNA was reduced by > 90% and piezo2 protein was not detectable. Piezo2-KO mice displayed no morphological abnormalities or altered cardiac function under nonstressed conditions. In a subsequent step, hearts of Piezo2-KO or WT-Cre+-mice were stressed by either three weeks of increased afterload (angiotensin II, 2.5 mg/kg/day) or one week of hypercontractility (isoprenaline, 30 mg/kg/day). As expected, angiotensin II treatment in WT-Cre+-mice resulted in higher heart and lung weight (per body weight, + 38%, + 42%), lower ejection fraction and cardiac output (- 30%, - 39%) and higher left ventricular anterior and posterior wall thickness (+ 34%, + 37%), while isoprenaline led to higher heart weight (per body weight, + 25%) and higher heart rate and cardiac output (+ 24%, + 54%). The Piezo2-KO mice reacted similarly with the exception that the angiotensin II-induced increases in wall thickness were blunted and the isoprenaline-induced increase in cardiac output was slightly less pronounced. As cardiac function was neither severely affected under basal nor under stressed conditions in Piezo2-KO mice, we conclude that piezo2 is not an indispensable mechanosensor in cardiomyocytes.
AB - A short-term increase in ventricular filling leads to an immediate (Frank-Starling mechanism) and a slower (Anrep effect) rise in cardiac contractility, while long-term increased cardiac load (e.g., in arterial hypertension) decreases contractility. Whether these answers to mechanical tension are mediated by specific sensors in cardiomyocytes remains elusive. In this study, the piezo2 protein was evaluated as a potential mechanosensor. Piezo2 was found to be upregulated in various rat and mouse cardiac tissues upon mechanical or pharmacological stress. To investigate its function, C57BL/6J mice with homozygous cardiomyocyte-specific piezo2 knockout [Piezo2-KO] were created. To this end, α-MHC-Cre mice were crossed with homozygous "floxed" piezo2 mice. α-MHC-Cre mice crossed with wildtype mice served as controls [WT-Cre+]. In cardiomyocytes of Piezo2-KO mice, piezo2 mRNA was reduced by > 90% and piezo2 protein was not detectable. Piezo2-KO mice displayed no morphological abnormalities or altered cardiac function under nonstressed conditions. In a subsequent step, hearts of Piezo2-KO or WT-Cre+-mice were stressed by either three weeks of increased afterload (angiotensin II, 2.5 mg/kg/day) or one week of hypercontractility (isoprenaline, 30 mg/kg/day). As expected, angiotensin II treatment in WT-Cre+-mice resulted in higher heart and lung weight (per body weight, + 38%, + 42%), lower ejection fraction and cardiac output (- 30%, - 39%) and higher left ventricular anterior and posterior wall thickness (+ 34%, + 37%), while isoprenaline led to higher heart weight (per body weight, + 25%) and higher heart rate and cardiac output (+ 24%, + 54%). The Piezo2-KO mice reacted similarly with the exception that the angiotensin II-induced increases in wall thickness were blunted and the isoprenaline-induced increase in cardiac output was slightly less pronounced. As cardiac function was neither severely affected under basal nor under stressed conditions in Piezo2-KO mice, we conclude that piezo2 is not an indispensable mechanosensor in cardiomyocytes.
KW - Angiotensin II/metabolism
KW - Animals
KW - Body Weight
KW - Ion Channels/genetics
KW - Isoproterenol/pharmacology
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Myocytes, Cardiac/metabolism
KW - Rats
U2 - 10.1038/s41598-022-12085-9
DO - 10.1038/s41598-022-12085-9
M3 - SCORING: Journal article
C2 - 35581325
VL - 12
JO - SCI REP-UK
JF - SCI REP-UK
SN - 2045-2322
IS - 1
M1 - 8193
ER -