Knockout of TRPV1 Exacerbates Left Ventricular Diastolic Dysfunction Induced by A High-fat Diet in Mice

Author(s): Beihua Zhong, Jack Rubinstein, Shuangtao Ma, Donna H. Wang*.

Journal Name: Cardiovascular & Hematological Disorders-Drug Targets

Volume 18 , Issue 3 , 2018

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Abstract:

Background: Transient Receptor Potential Vanilloid 1 (TRPV1) channels in sensory nerves have anti-oxidative properties and counteract obesity and diabetes that are associated with diastolic dysfunction with preserved ejection fraction. We tested the hypothesis that TRPV1 knockout exacerbates high-fat diet (HFD)-induced glucose intolerance and diastolic dysfunction.

Method: Trpv1-/- and wild-type (WT) mice were fed chow diet or HFD for 20 weeks. Then, we performed the intraperitoneal glucose tolerance test, measured the heart function through transthoracic echocardiography and Langendorff heart perfusion system, analyzed cardiac histology, and measured the myocardial superoxide production and the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases.

Results: HFD increased body weight, heart weight, and levels of fasting glucose, insulin, and leptin in both strains, with no differences between two strains. HFD impaired glucose tolerance in both strains with a more profound effect on Trpv1-/- than WT mice. HFD increased left ventricular (LV) internal diameter in diastole in both strains, while increased LV posterior wall thickness in diastole in Trpv1-/- but not in WT mice. HFD increased LV end-diastolic pressure in both strains with a further increase in Trpv1-/- mice, while decreased -dP/dt in Trpv1-/- but not in WT mice. HFDinduced cardiac collagen deposition and superoxide production were enhanced in Trpv1-/- mice. HFD upregulated cardiac p22phox in both strains, while increased p47phox in Trpv1-/- but not in WT mice.

Conclusion: In summary, TRPV1 knockout exacerbates HFD-induced glucose intolerance, cardiac oxidative stress and collagen deposition, leading to aggravated LV diastolic dysfunction.

Keywords: TRPV1, obesity, high fat intake, diastolic dysfunction, oxidative stress, diabetes.

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Article Details

VOLUME: 18
ISSUE: 3
Year: 2018
Page: [215 - 223]
Pages: 9
DOI: 10.2174/1871529X18666180503124538
Price: $58

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