title: Decreased Polycystin 2 Levels Result in Non-Renal Cardiac Dysfunction with Aging.
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.
authors.affiliation: Department of Pharmacology, Yale University New Haven, Connecticut, United States of America.
authors.forename: Ivana Y
authors.initials: IY
authors.lastname: Kuo
authors.affiliation: Department of Pharmacology, Yale University New Haven, Connecticut, United States of America.
authors.forename: Sophie L
authors.initials: SL
authors.lastname: Duong
authors.affiliation: Department of Pharmacology, Yale University New Haven, Connecticut, United States of America.
authors.forename: Lily
authors.initials: L
authors.lastname: Nguyen
authors.affiliation: Department of Pharmacology, Yale University New Haven, Connecticut, United States of America.|Department of Cellular and Molecular Physiology, Yale University, New Haven, Connecticut, United States of America.
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Ehrlich
mesh_terms: D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004837:Epinephrine / Q000378:metabolism; D005786:Gene Expression Regulation; D006321:Heart / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009638:Norepinephrine / Q000378:metabolism; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics; D015398:Signal Transduction; D050396:TRPP Cation Channels / Q000172:deficiency / Q000378:metabolism*
chemical_list: D004837:Epinephrine; D009638:Norepinephrine; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D050396:TRPP Cation Channels