Ahmadieh S. Clin Sci (Lond). 2020 Jan 17;134(1):3-13.
A fundamental origin of cardio-metabolic disorder is the quality and distribution of adipose tissue as some obese patients are metabolically healthy. The extent of inflammation of adipose tissue exhibited insulin resistance and systemic metabolic disorder causes obesity-related risk; therefore, the local effect of perivascular adipose tissue (PVAT) on vascular disorder is considered. PVAT development and chemokine production showed high level of inflammation that likely plays an important role in the pathogenesis of CVD in the hyperlipidemic, atherosclerosis-prone animal models and human arteries. In healthy conditions, PVAT seems to play a protective role in modulating metabolism, inflammation, and function of correlated blood vessels. But, their effect on CVD, especially in humans, is yet to be fully explained. Thus, Ahmadieh S et al., conducted a review to focus on the complex procedures whereby PVAT modulates atherosclerosis, with a significance on clinical involvement of PVAT and arising strategies for analysis and therapy of CVD based on PVAT biology.
Human epicardial adipose tissue separated from patients gone through coronary artery bypass grafting surgery showed substantially greater levels of chemokines (i.e. MCP-1) and inflammatory cytokines [i.e. interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α] as compared to subcutaneous adipose tissue gained from the same patients. Vice versa, in patients with crucial coronary atherosclerosis, anti-inflammatory adiponectin expression was found to be substantially lower in epicardial fat samples as compared to those without, recommending an imbalance in PVAT inflammation in the atherosclerosis. The epicardial portion of human coronary arteries is both richly equiped in PVAT and especially exposed to atherosclerosis. PVAT also had endogenous anti-inflammatory pathways that may restrict the level of local inflammation. LRP1 dysfunction in the liver, smooth muscle cells (SMCs), and macrophages increases atherosclerosis. LRP1-deficient PVAT showed a pro-inflammatory phenotype and increased resistin expression. Additionally, transplantation of LRP1-deficient PVAT to the carotid artery generated a three-fold elevation in atherosclerosis development as compared to control, correlated with enhanced macrophage recruitment and MCP-1, IL-6, and TNF-α expression. Healthy PVAT may be home to immune cells that reduced atherosclerosis progress. Human coronary PVAT showed that B cells were elevated in close proximity to the coronary artery in fat-correlated lymphoid clusters. Particularly, levels of IgM were inversely correlated with MCP-1 levels to oxidation-specific epitopes on LDL in the plasma and with the progress of atherosclerosis in humans. In a murine type 2 diabetes mellitus (T2DM) model, the increase in arterial tone because of chronic inflammation and vascular dysfunction was associated with DC accumulation in PVAT, and DC reduction exhibited a critical role of DC in PVAT inflammation associated with atherosclerosis with the increase in both the vascular dysfunction and pro-inflammatory environment. Transplanted PVAT showed increased TGF-β1 mRNA expression, and positive TGF-β1 immunostaining co-localizing with M2-like macrophages. This remote anti-atherogenic effect of transplanted PVAT was counteracted with the administration of TGF-β1 antibody injections, suggesting that patients with advanced atherosclerosis exhibited substantial reduction in circulating active TGF-β1. PVAT could play a previously unrecognized but important role in proliferation of vasa vasorum in atherosclerosis as adipose tissue is inherently angiogenic. Furthermore, perivascular adipocytes may be uniquely poised to upgrade angiogenesis causes vasa vasorum proliferation. Inclusion of the PVAT FAI may represent a promising method in the standard coronary CT evaluation to measure coronary inflammation and spot the beginning of primary or intensive secondary prevention strategies for those patients who were not recognized with traditional CV risk factors.
Thus, it was concluded that PVAT may delivered as an auspicious target for atherosclerosis interferences and therapies. PVAT FAI is an appealing prospective strategy to enhance PVAT function and more studies are needed to understand the therapeutic indications and to confirm these findings in humans.
Figure 1: Proposed mechanisms whereby PVAT modulates vascular function and atherosclerotic development
CVD: Cardiovascular Disease; TGF: Transforming Growth Factor; Dc: Dendritic Cells
