Perivascular Adipose Tissue Potentiates Contraction of Coronary Vascular Smooth Muscle

Abstract

Background This investigation examined the mechanisms by which coronary perivascular adipose tissue (PVAT)-derived factors influence vasomotor tone and the PVAT proteome in lean vs. obese swine. Methods and Results Coronary arteries from Ossabaw swine were isolated for isometric tension studies. We found that coronary (P=0.03) and mesenteric (P=0.04), but not subcutaneous adipose tissue, augmented coronary contractions to KCl (20 mM). Inhibition of CaV1.2 channels with nifedipine (0.1 μM) or diltiazem (10 μM) abolished this effect. Coronary PVAT increased baseline tension and potentiated constriction of isolated arteries to PGF2α in proportion to the amount of PVAT present (0.1–1.0 g). These effects were elevated in tissues obtained from obese swine and were observed in intact and endothelium denuded arteries. Coronary PVAT also diminished H2O2-mediated vasodilation in lean, and to a lesser extent in obese arteries. These effects were associated with alterations in the obese coronary PVAT proteome (detected 186 alterations) and elevated voltage-dependent increases in intracellular [Ca2+] in obese smooth muscle cells. Further studies revealed that a Rho-kinase inhibitor fasudil (1 μM) significantly blunted artery contractions to KCl and PVAT in lean, but not obese swine. Calpastatin (10 μM) also augmented contractions to levels similar to that observed in the presence of PVAT. Conclusions Vascular effects of PVAT vary according to anatomic location and are influenced by an obese phenotype. Augmented contractile effects of obese coronary PVAT are related to alterations in the PVAT proteome (e.g. calpastatin), Rho-dependent signaling, and the functional contribution of K+ and CaV1.2 channels to smooth muscle tone.

Sustained release nitrite therapy results in myocardial protection in a porcine model of metabolic syndrome with peripheral vascular disease

“…In the present study, LAD coronary arteries obtained from obese OS had attenuated contraction to KCl and PGF 2␣ compared with Yorkshire nonischemic lean control swine with no significant difference between CLI ϩ SR-nitrite-and CLI ϩ placebo-treated groups. Similar to our findings, Owen et al (38) concluded that obesity augments Ca 2ϩ cycling and smooth muscle vasoconstriction after observing an attenuated contraction in obese OS coronaries compared with lean control arteries. Using vasodilators that induce relaxation through endothelium-independent (SNP) and endothelium-dependent (substance P and bradykinin) mechanisms, we examined the vascular reactivity of LAD coronary arteries obtained from CLI ϩ SR-nitrite-treated pigs, CLI ϩ placebotreated pigs, and nonischemic lean control pigs.…”

Maternal High-Fat Diet Exaggerates Atherosclerosis in Adult Offspring by Augmenting Periaortic Adipose Tissue-Specific Proinflammatory Response

“…[21][22][23][24][25] Takaoka et al found elevated expression of proinflammatory genes and lower adiponectin expression in the perivascular adipose tissue of obese mice and concluded that this contributed to exaggerated neointimal formation after arterial injury. 26 Chatterjee et al also found elevated proinflammatory gene expression and diminished adiponectin expression in the perivascular adipose tissue surrounding diseased human coronary arteries.…”

Involvement of NADPH oxidase in A2A adenosine receptor-mediated increase in coronary flow in isolated mouse hearts

“…H 2 O 2 , a molecule within the reactive oxygen species (ROS) family, has been proposed to serve as a pivotal vasodilator in coronary flow regulation in human, canine, porcine, and murine coronary vasculature [19,[22][23][24][25][26]. NADPH oxidases (Nox) are the major source of ROS in the vasculature that plays both physiological and pathophysiological roles in the control of vascular tone [27][28][29].…”