Invited commentary

Abstract

Perivascular adipose tissue (PVAT) is an important supportive component to vessels. Over the years, PVAT has gained much attention owing to its likely involvement in cardiovascular diseases such as atherosclerosis. The incongruous effects of PVAT—positive vs negative—on atherosclerosis necessitate studies such as the one presented here by Ren et al.1Ren L. Wang L. You T. Liu Y. Wu F. Zhu L. et al.Perivascular adipose tissue modulates carotid plaque formation induced by disturbed flow in mice.J Vas Surg. 2019; 70: 927-936Abstract Full Text Full Text PDF Scopus (5) Google Scholar In the current study, the authors investigated the effect of transplanted PVAT (PVAT-T) on atherosclerotic plaque formation in a carotid ligation model of Apoe-/- mice under a high-fat diet. This is an effective approach in that it allows the examination of PVAT in a vascular bed that is normally free of PVAT. Using this model, the authors first established that PVAT could be induced in the adventitia of carotids by disturbed flow. The induced carotid PVAT showed a similar expression profile of adipose genes to PVAT native to thoracic aorta. This characterization is essential considering the heterogeneity of PVAT, which is influenced greatly by anatomic location and can resemble both white and brown adipose tissue. Interestingly, the authors found that inhibition of PVAT in their disturbed flow model using a peroxisome proliferator activated receptor-γ inhibitor exacerbated atherosclerotic plaque formation. This is similar to the findings by Chang et al2Chang L. Villacorta L. Li R. Hamblin M. Xu W. Dou C. et al.Loss of perivascular adipose tissue on peroxisome proliferator-activated receptor-γ deletion in smooth muscle cells impairs intravascular thermoregulation and enhances atherosclerosis.Circulation. 2012; 126: 1067-1078Crossref PubMed Scopus (207) Google Scholar showing the atheroprotective effects of PVAT. Furthermore, the authors found that transplanting thoracic aortic PVAT from wild-type mice to mice that received partial carotid ligation reduced the plaque size compared with mice receiving PVAT-T from Apoe-/- donors. These findings underscore the importance of characterizing and using various sources of PVAT to determine its role in vascular disease. The authors show that mice receiving PVAT-T from Apoe-/- donors have higher plaque macrophage infiltration compared with PVAT-T from wild-type mice. They suggest that this effect is due to the higher proinflammatory levels of MCP-1 in PVAT-T in Apoe-/- engraftment. Although the authors' assertion is in line with the literature on the paracrine capacity of PVAT,3Qi X.Y. Qu S.L. Xiong W.H. Rom O. Chang L. Jiang Z.S. Perivascular adipose tissue (PVAT) in atherosclerosis: a double-edged sword.Cardiovasc Diabetol. 2018; 17: 134Crossref PubMed Scopus (48) Google Scholar, 4Akoumianakis I. Antoniades C. The interplay between adipose tissue and the cardiovascular system: is fat always bad?.Cardiovasc Res. 2017; 113: 999-1008Crossref PubMed Scopus (60) Google Scholar, 5Aghamohammadzadeh R. Withers S. Lynch F. Greenstein A. Malik R. Heagerty A. Perivascular adipose tissue from human systemic and coronary vessels: the emergence of a new pharmacotherapeutic target.Br J Pharmacol. 2012; 165: 670-682Crossref PubMed Scopus (69) Google Scholar it lacks a critical piece of data of the characterization of PVAT-T from respective donors before transplantation. Without the knowledge of baseline PVAT-T macrophage content, it is difficult to deduce whether plaque macrophage infiltration is due to the paracrine effect of the PVAT-T or the macrophage migration out of PVAT-T. Additionally, future studies will be necessary to identify the cellular source of inflammatory molecules from the engraftment tissue used in these studies. The findings presented in this article using the novel approach of combining carotid ligation with PVAT transplantation support both the protective and pathological potential of PVAT. Several key questions remain regarding the function of PVAT both in homeostasis and disease. Studies such as these are important for paving the way for understanding the cross-talk between PVAT and the vasculature. Investigation of the signaling mechanisms underlying how PVAT influences the vessel wall or vice versa are crucial to understanding complex diseases such as atherosclerosis. Perivascular adipose tissue modulates carotid plaque formation induced by disturbed flow in miceJournal of Vascular SurgeryVol. 70Issue 3PreviewEmerging evidence shows that perivascular adipose tissue (PVAT) is crucially involved in inflammation and cardiovascular diseases. However, controversial results have been reported regarding the effect of PVAT in atherosclerosis. This study aimed to determine the role of PVAT in disturbed blood flow (d-flow)-induced carotid plaque formation. Full-Text PDF Open Archive