Differential Phenotypes in Perivascular Adipose Tissue Surrounding the Internal Thoracic Artery and Diseased Coronary Artery

Abstract

Background Perivascular adipose tissue ( PVAT ) is causally associated with vascular function and the pathogenesis of vascular disease in association with metabolically driven chronic inflammation called metaflammation. However, the difference in PVAT surrounding the coronary artery ( CA ‐ PVAT ) and that surrounding the internal thoracic artery (ITA‐PVAT), a vessel resistant to atherosclerosis, remains unclear. Herein, we investigated whether CA ‐ PVAT , ITA ‐ PVAT , and subcutaneous adipose tissue ( SCAT ) have distinct phenotypes. Methods and Results Fat pads were sampled from 44 patients (men/women, 36:8; age, 67±13 years) with CA disease who underwent elective CA bypass grafting. Adipocyte size in ITA ‐ PVAT and that in CA ‐ PVAT were significantly smaller than that in SCAT . A greater extent of fibrosis and increased gene expression levels of fibrosis‐related molecules were observed in CA ‐ PVAT than those in SCAT and those in ITA ‐ PVAT . CA ‐ PVAT exhibited more pronounced metaflammation, as indicated by a significantly larger extent of CD 68‐positive and CD 11c‐positive M1 macrophages, a lower ratio of CD 206‐positive M2 to CD 11c‐positive M1 macrophages, a lower gene expression level of adiponectin, and higher gene expression levels of inflammatory cytokines and inflammasome‐ and endoplasmic reticulum stress–related molecules, than did ITA ‐ PVAT and SCAT . Expression patterns of adipocyte developmental and pattern‐forming genes were totally different among SCAT , ITA ‐ PVAT, and CA ‐ PVAT . Conclusions The phenotype of ITA ‐ PVAT is closer to that of SCAT than that of CA ‐ PVAT , which may result from inherent differences in adipocytes. ITA ‐ PVAT appears to be protected from metaflammation and consecutive adipose tissue remodeling, which may contribute to the decreased atherosclerotic plaque burden in the ITA.

Serum leptin, a potential predictor of long‐term angiographic progression in Takayasu’s arteritis

“…In rodents, the composition of PVAT varies in different places, such as brown AT surrounding thoracic aorta and white AT surrounding mesenteric artery . In humans, PVAT is basically more akin to white AT than brown AT in morphology, and so far its heterogeneity in humans has not been studied as well as that in rodents, but a recent study of the coronary artery and internal thoracic artery hints that differential phenotypes of PVAT may lead to vascular lesions in specific areas . PVAT is characterized by small adipocytes with multiple small lipid droplets, vascular regulation, and interplay with immune cells .…”

Perivascular adipose tissue in cardiovascular diseases – an update

“…Macrophage phenotype is particular in coronary PVAT, being different from thoracic aorta and subcutaneous tissue associated PVAT (37). Thus, they exhibit a lower ratio of CD206-positive M2 to CD11c-positive M1 macrophages, along with a significantly larger extent of CD11c-positive M1 macrophages, and an enhanced gene expression of a panel of inflammatory cytokines, such as IL-6, IL-1b, TNF-α, and MCP-1 (37). Moreover, the differences are related to an increased fibrosis, along with a decreased gene expression of anti-inflammatory adipokines (e.g., adiponectin), and an increased activation of inflammasomes and endoplasmic reticulum stress (37).…”

“…Macrophage phenotype is particular in coronary PVAT, being different from thoracic aorta and subcutaneous tissue associated PVAT (37). Thus, they exhibit a lower ratio of CD206-positive M2 to CD11c-positive M1 macrophages, along with a significantly larger extent of CD11c-positive M1 macrophages, and an enhanced gene expression of a panel of inflammatory cytokines, such as IL-6, IL-1b, TNF-α, and MCP-1 (37).…”

“…Although the data related to the relationship between human PVAT and atheromatosis are more limited, a recent study performed on 44 patients with a coronary bypass revealed that the adipocytes associated with the thoracic aorta and coronary arteries are significantly smaller than those comprising the subcutaneous tissue (37).…”

“…Thus, they exhibit a lower ratio of CD206-positive M2 to CD11c-positive M1 macrophages, along with a significantly larger extent of CD11c-positive M1 macrophages, and an enhanced gene expression of a panel of inflammatory cytokines, such as IL-6, IL-1b, TNF-α, and MCP-1 (37). Moreover, the differences are related to an increased fibrosis, along with a decreased gene expression of anti-inflammatory adipokines (e.g., adiponectin), and an increased activation of inflammasomes and endoplasmic reticulum stress (37). Nowadays, all of these observations support the PVAT's active role in the initiation and progression of atheromatous coronary lesions and of ischemic coronary disease, encompassing the vascular support role that has been previously attributed to this tissue.…”