Cardiac Remodeling in Cardiomyocyte-Specific PIEZO2 Knock-Out Mice

Objectives: Mechanosensation and mechanotransduction belong to the most fundamental processes in biology. Especially in the cardiovascular system a mechanosensitive feedback mechanism is essential to adapt to different physiological demands. Piezo2 is a mechanosensitive ion channel and has a role in rapidly adapting mechanically activated currents in somatosensory neurons. Its expression in cardiac tissue is low but stable detectable and we found a significant increase of Piezo2 expression in heart tissue of mice 2 weeks after transverse aortic constriction (TAC) and 3 weeks after continuous angiotensin II infusion in comparison with the control groups. Also in engineered heart tissue model of cardiac hypertrophy we found a rise of Piezo2 expression.

Methods: To investigate the role of piezo2 in cardiomyocytes we engineered cardiomyocyte-specific piezo2 knockout mice using the Cre-lox technology. In the next step we investigated whether the piezo2-knock out in cardiomyocytes led to the eradication of piezo2-mRNA. To this end cardiomyocytes from wild type and knockout mice were isolated in a Langendorff heart perfusion setup and purified by albumin gradient centrifugation. Subsequently we exposed wild type and knockout mice to two different pharmacological cardiac stress regimens. In the first arm of the study, angiotensin II was employed for 3 weeks. In the second arm, isoprenaline was employed for 1 week.

Result: The breeding of piezo2 knockout mice was successful. Only traces of piezo2-mRNA could be detected in cardiomyocytes of these mice. Piezo2 knockout mice displayed no morphological or behavioral abnormalities under non-stressed conditions and had a normal life expectancy. No functional or morphological difference to wild-type mice could be observed in echocardiography. Also after pharmacological intervention we could not find differences between wild-type and knockout mice in heart weight body weight ratio and echocardiographic findings.

Conclusion: We found an increase of Piezo2 expression in heart tissue in different models of cardiac hypertrophy. A cardiomyocyte specific piezo2 knock out mouse has a normal phenotype and life expectancy. Cardiac remodeling under stress condition is similar to wild type mice. Piezo2 seems to play a role in mechanosensation of the heart but has no effect on the development of cardiac hypertrophy.

No conflict of interest has been declared by the author(s).

Publication History

Article published online:
19 February 2021