Pericardial Adipose Tissue Thrombospondin-1 Associates With Antiangiogenesis in Ischemic Heart Disease

• Published in: The American journal of cardiology Vol. 210; pp. 201 - 207
• Main Authors: Ahmed, Bulbul, Farb, Melissa G., Karki, Shakun, D'Alessandro, Sophia, Edwards, Niloo M., Gokce, Noyan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2024; Elsevier Limited
• Subjects: Adipose Tissue; Aged; Angiogenesis; Angiopoietin; Antiangiogenics; Aorta; Aortic aneurysms; Body fat; Body mass index; Body size; Cardiovascular disease; Cholesterol; Cholesterol, LDL - metabolism; coronary artery bypass grafting; Coronary artery disease; Coronary Artery Disease - etiology; Coronary vessels; Endostatin; Enzymes; Fibroblast growth factor 2; Gene expression; Growth factors; Heart diseases; Heart surgery; Humans; Ischemia; Kinases; Low density lipoprotein; Microvasculature; Middle Aged; Myocardial Ischemia - complications; obesity; Paracrine signalling; pericardial adipose tissue; Pericardium; Polymerase chain reaction; Polymerization; Protein-tyrosine kinase; Proteins; Regression analysis; RNA, Messenger - metabolism; Thrombospondin; Thrombospondin 1 - genetics; Thrombospondin 1 - metabolism; Triglycerides; Tyrosine; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; Vascularization; United States > US; Massachusetts; coronary artery disease; angiogenesis; obesity; pericardial adipose tissue; coronary artery bypass grafting
• DOI: 10.1016/j.amjcard.2023.09.104
• ISSN: 0002-9149; 1879-1913

Accumulation of ectopic pericardial adipose tissue has been associated with cardiovascular complications which, in part, may relate to adipose-derived factors that regulate vascular responses and angiogenesis. We sought to characterize adipose tissue microvascular angiogenic capacity in subjects who underwent elective cardiac surgeries including aortic, valvular, and coronary artery bypass grafting. Pericardial adipose tissue was collected intraoperatively and examined for angiogenic capacity. Capillary sprouting was significantly blunted (twofold, p <0.001) in subjects with coronary artery disease (CAD) (age 60 ± 9 years, body mass index [BMI] 32 ± 4 kg/m2, low-density lipoprotein cholesterol [LDL-C] 95 ± 46 mg/100 ml, n = 29) compared with age-, BMI-, and LDL-C matched subjects without angiographic obstructive CAD (age 59 ± 10 y, BMI 35 ± 9 kg/m2, LDL-C 101 ± 40 mg/100 ml, n = 12). For potential mechanistic insight, we performed mRNA expression analyses using quantitative real-time polymerase chain reaction and observed no significant differences in pericardial fat gene expression of proangiogenic mediators vascular endothelial growth factor-A (VEGF-A), fibroblast growth factor-2 (FGF-2), and angiopoietin-1 (angpt1), or anti-angiogenic factors soluble fms-like tyrosine kinase-1 (sFlt-1) and endostatin. In contrast, mRNA expression of anti-angiogenic thrombospondin-1 (TSP-1) was significantly upregulated (twofold, p = 0.008) in CAD compared with non-CAD subjects, which was confirmed by protein western-immunoblot analysis. TSP-1 gene knockdown using short hairpin RNA lentiviral delivery significantly improved angiogenic deficiency in CAD (p <0.05). In conclusion, pericardial fat in subjects with CAD may be associated with an antiangiogenic profile linked to functional defects in vascularization capacity. Local paracrine actions of TSP-1 in adipose depots surrounding the heart may play a role in mechanisms of ischemic heart disease.