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TRPV1 Activation Counters Vascular Dysfunction by Increasing PPARs, SiRT-1, PGC-1α and UCP-1 Expression in the Thoracic Aorta

posted on 26.06.2017, 00:00 by Kaylan Schilling, Laurel Markret, Joy Watkins, Kelvin Kinyatta
Obesity foreshadows metabolic diseases. The imbalance between energy intake and expenditure leads to increased visceral fat accumulation, causing obesity. Vascular dysfunction associated obesity causes hypertension and progressively leads to cardiovascular diseases. Recent research suggests that activating TRPV1 is a good strategy to counter obesity and metabolic complications. In this work, we evaluated a hypothesis that activation of transient receptor potential vanilloid subfamily 1 (TRPV1) expressed in the thoracic aorta vasculature suppresses development of hypertension and vascular damage by enhancing expression of metabolically important peroxisome proliferator activated receptors (PPARs), sirtuin-1 (SiRT-1; central cellular metabolic sensor), PPARγ coactivator 1α (PGC-1α) and uncoupling protein 1 (UCP-1). Data show high fat diet (HFD; 60% calories from fat) feeding caused obesity and hypertension and suppressed the expression of PPARs, SiRT-1, PGC-1α and mitochondrial UCP-1. Capsaicin (a TRPV1 agonist) supplementation reversed this. Capsaicin increased the expression of SiRT-1, PPARγ, PGC-1α and UCP-1 in the thoracic aorta of wild type mice but not TRPV1-/- mice. Further, capsaicin enhanced expression of PKCε, which in turn enhanced the phosphorylation of PPARα. Also, capsaicin significantly decreased elevated systolic and diastolic blood pressure (measured by non-invasive tail cuff method) in wild type but not in TRPV1-/- mice. Data show that HFD significantly suppressed expression of TRPV1 in the thoracic aorta and capsaicin countered this. Our data collectively suggest that activation of TRPV1 tightly couples to a SiRT-1-PPARs and PGC-1-dependent signaling mechanism to upregulate mitochondrial UCP-1 to protect vascular damage.



Baskaran, Thyagarajan Baskaran, Padmamalini McAllister, Steve






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