The role of transient receptor potential vanilloid 2 channel in cardiac aging.
BACKGROUND
The aging heart is characterized by cellular and molecular changes leading to a decline in physiologic function and cardiac remodeling, specifically the development of myocyte hypertrophy and fibrosis. Transient receptor potential vanilloid 2 (TRPV2), a stretch-mediated channel and regulator of calcium homeostasis, plays a key role in the function and structure of the heart. TRPV2 also plays an important role in the adaptive and maladaptive compensatory mechanisms of the heart in response to pathologic and exercise-induced stress. Our current study seeks to elucidate the potential role of TRPV2 channels in the regulation of cardiac function in aging.


METHODS
Wild-type (WT) and TRPV2 functional knockout (FKO) mice were aged out to various time points, and their cardiac function was measured using advanced echocardiography. Furthermore, we histologically analyzed the heart morphology to determine myocyte hypertrophy, the development of fibrosis and the relative expression of TRPV2.


RESULTS
Our results demonstrate that even though TRPV2-FKO mice have impaired function at baseline, their cardiac function as measured via standard and advanced echocardiographic parameters (ejection fraction, cardiac output and circumferential strain) decreased less with aging in comparison with the WT group. Furthermore, there was less fibrosis and hypertrophy in the TRPV2-FKO group with aging in comparison with the WT. The expression of TRPV2 in the WT group did not significantly change with aging.


CONCLUSIONS
TRPV2 functional deletion is compatible with aging and associated with a decreased development of myocyte hypertrophy and fibrosis. It may be an important target for prevention of age-induced cardiac remodeling.
Department of Internal Medicine, Division of Cardiovascular Diseases, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML0542, Cincinnati, OH, 45267, USA.
Shannon
S
Jones
Department of Internal Medicine, Division of Cardiovascular Diseases, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML0542, Cincinnati, OH, 45267, USA.
Adrien
A
Mann
Department of Internal Medicine, Division of Cardiovascular Diseases, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML0542, Cincinnati, OH, 45267, USA.
Mariah C
MC
Worley
Department of Pathobiology, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA.
Logan
L
Fulford
Department of Nutritional Sciences College of Allied Health, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA.
David
D
Hall
Department of Internal Medicine, Division of Cardiovascular Diseases, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML0542, Cincinnati, OH, 45267, USA.
Rajiv
R
Karani
Department of Internal Medicine, Division of Cardiovascular Diseases, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML0542, Cincinnati, OH, 45267, USA.
Min
M
Jiang
Department of Internal Medicine, Division of Cardiovascular Diseases, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML0542, Cincinnati, OH, 45267, USA.
Nathan
N
Robbins
Department of Internal Medicine, Division of Cardiovascular Diseases, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML0542, Cincinnati, OH, 45267, USA.
Jack
J
Rubinstein
Department of Internal Medicine, Division of Cardiovascular Diseases, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML0542, Cincinnati, OH, 45267, USA. sheryl.koch@uc.edu.
Sheryl E
SE
Koch
D000818:Animals; D004452:Echocardiography / Q000379:methods*; D005260:Female; D005355:Fibrosis; D006321:Heart / Q000503:physiopathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D050916:TRPV Cation Channels / Q000235:genetics*
D050916:TRPV Cation Channels
Cardiac aging; Cardiac function; TRPV2; Ventricular remodeling