| First Author | Kuo IY | Year | 2016 |
| Journal | PLoS One | Volume | 11 |
| Issue | 4 | Pages | e0153632 |
| PubMed ID | 27081851 | Mgi Jnum | J:249085 |
| Mgi Id | MGI:6092577 | Doi | 10.1371/journal.pone.0153632 |
| Citation | Kuo IY, et al. (2016) Decreased Polycystin 2 Levels Result in Non-Renal Cardiac Dysfunction with Aging. PLoS One 11(4):e0153632 |
| abstractText | 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 beta-adrenergic responses, the 9 month old Pkd2+/- mice exhibited a stronger contractile response, which also coincided with preserved localization of the beta2 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. |
