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PLoS One. 2016 Apr 15;11(4):e0153632. doi: 10.1371/journal.pone.0153632. eCollection 2016.

Decreased Polycystin 2 Levels Result in Non-Renal Cardiac Dysfunction with Aging.

Author information

1
Department of Pharmacology, Yale University New Haven, Connecticut, United States of America.
2
Department of Cellular and Molecular Physiology, Yale University, New Haven, Connecticut, United States of America.

Abstract

Mutations in the gene for polycystin 2 (Pkd2) lead to polycystic kidney disease, however the main cause of mortality in humans is cardiac related. We previously showed that 5 month old Pkd2+/- mice have altered calcium-contractile activity in cardiomyocytes, but have preserved cardiac function. Here, we examined 1 and 9 month old Pkd2+/- mice to determine if decreased amounts of functional polycystin 2 leads to impaired cardiac function with aging. We observed changes in calcium handling proteins in 1 month old Pkd2+/- mice, and these changes were exacerbated in 9 month old Pkd2+/- mice. Anatomically, the 9 month old Pkd2+/- mice had thinner left ventricular walls, consistent with dilated cardiomyopathy, and the left ventricular ejection fraction was decreased. Intriguingly, in response to acute isoproterenol stimulation to examine β-adrenergic responses, the 9 month old Pkd2+/- mice exhibited a stronger contractile response, which also coincided with preserved localization of the β2 adrenergic receptor. Importantly, the Pkd2+/- mice did not have any renal impairment. We conclude that the cardiac-related impact of decreased polycystin 2 progresses over time towards cardiac dysfunction and altered adrenergic signaling. These results provide further evidence that polycystin 2 provides a critical function in the heart, independent of renal involvement.

PMID:
27081851
PMCID:
PMC4833351
DOI:
10.1371/journal.pone.0153632
[Indexed for MEDLINE]
Free PMC Article

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