Perivascular Adipose Tissue Potentiates Contraction of Coronary Vascular Smooth Muscle: Influence of Obesity

• Published in: Circulation (New York, N.Y.) Vol. 128; no. 1; pp. 9 - 18
• Main Authors: Owen, Meredith Kohr, Witzmann, Frank A, McKenney, Mikaela L, Lai, Xianyin, Berwick, Zachary C, Moberly, Steven P, Alloosh, Mouhamad, Sturek, Michael, Tune, Johnathan D
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Wolters Kluwer Health | Lippincott Williams & Wilkins 02.07.2013; Lippincott Williams & Wilkins
• Subjects: Animals; Biological and medical sciences; Blood and lymphatic vessels; Body Weight - physiology; Calcium-Binding Proteins - pharmacology; Cardiology. Vascular system; Coronary Artery Disease - pathology; Coronary Artery Disease - physiopathology; Coronary heart disease; Coronary Vessels - physiopathology; Cysteine Proteinase Inhibitors - pharmacology; Disease Models, Animal; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Heart; Intra-Abdominal Fat - pathology; Intra-Abdominal Fat - physiopathology; Isometric Contraction - drug effects; Isometric Contraction - physiology; Medical sciences; Mesenteric Arteries - physiopathology; Metabolic diseases; Muscle, Smooth, Vascular - pathology; Muscle, Smooth, Vascular - physiopathology; Obesity; Obesity - pathology; Obesity - physiopathology; Proteomics; Subcutaneous Fat - pathology; Subcutaneous Fat - physiopathology; Sus scrofa; Vasoconstriction - drug effects; Vasoconstriction - physiology; Obesity; Adipose tissue; muscle, smooth; Nutrition disorder; Coronary artery; Vasoconstriction; Smooth muscle; Cardiovascular disease; Coronary heart disease; Contraction; coronary disease; Vasomotricity; Blood vessel; Circulatory system; Cardiology; Nutritional status; adipose tissue; vasoconstriction; obesity
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.112.001238

BACKGROUND—This investigation examined the mechanisms by which coronary perivascular adipose tissue (PVAT)–derived factors influence vasomotor tone and the PVAT proteome in lean versus 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 mmol/L). Inhibition of CaV1.2 channels with nifedipine (0.1 µmol/L) or diltiazem (10 µmol/L) abolished this effect. Coronary PVAT increased baseline tension and potentiated constriction of isolated arteries to prostaglandin F2α 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 [Ca] in obese smooth muscle cells. Further studies revealed that the Rho-kinase inhibitor fasudil (1 µmol/L) significantly blunted artery contractions to KCl and PVAT in lean but not obese swine. Calpastatin (10 μmol/L) 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 (eg, calpastatin), Rho-dependent signaling, and the functional contribution of K and CaV1.2 channels to smooth muscle tone.