Leptin-Dependent and Leptin-Independent Paracrine Effects of Perivascular Adipose Tissue on Neointima Formation

Abstract

Our findings suggest that locally elevated leptin levels may promote neointima formation, independent of obesity and systemic hyperleptinemia, but also underline the importance of perivascular inflammation in mediating the increased cardiovascular risk in obesity.

Differences between perivascular adipose tissue surrounding the heart and the internal mammary artery: possible role for the leptin-inflammation-fibrosis-hypoxia axis

“…However, little is known about the factors mediating the local, presumably detrimental 'paracrine' effects of PVAT on the vessel wall. Some of the few experimental studies available reported that PVAT transplantation may induce [42], possibly due to reduced expression of adiponectin [43], or the increased production of TNFa [44], MCP1 [45], or leptin [22].…”

“…Leptin receptors are expressed on cells within the blood vessel wall and atherosclerotic lesions [18], and experimental work from our group and others has revealed a role for leptin in the pathophysiology of cardiovascular events by promoting thrombosis [19], neointima formation [20], and atherosclerosis [21]. Recently, we could show that perivascular leptin overexpression is sufficient to mediate neointimal hyperplasia in mice, and that this effect is independent of body weight and circulating leptin levels [22]. However, despite the accumulating evidence on the cardiovascular effects of leptin, only few studies have so far examined the association of perivascular leptin expression with human atherosclerosis.…”

Telmisartan Ameliorates Nephropathy in Metabolic Syndrome by Reducing Leptin Release From Perirenal Adipose Tissue

“…Combined with our results showing that Ang II stimulates leptin release from VAs by activating the AT1R-ERK1/2 pathway, these observations suggest that Ang(1-7) antagonizes the effect of the Ang II-AT1R axis via activation of the Mas receptor-PI3K-Akt pathway. ACE2 cleaves Ang II to yield Ang (1)(2)(3)(4)(5)(6)(7) and is the rate-limiting enzyme in this conversion. 18 We speculate that ACE2 is the key component that negatively regulates leptin release; further experiments are necessary to confirm this hypothesis.…”

“…Another portion of PRAT was fixed in 10% paraformaldehyde, dehydrated, embedded in paraffin, and cut into four μm slices for H&E staining. Adipocyte size was determined by capturing bright field images and measuring 200 cells from each rat 4 . Quantitative Real-time RT-PCR The levels of mRNA encoding the renal cortical tissue leptin receptor, AT1R, adiponectin, and inflammatory cytokines in PRAT or adipocytes were determined by quantitative real-time RT-PCR.…”

“…1 MetS is often accompanied by visceral adipose tissue (VAT) accumulation and dysfunction, along with elevated production of VATderived adipocytokines, and adipocytokines derived from perivascular adipose tissue have been implicated in the vascular lesions associated with MetS. [2][3][4] Thus, in addition to common risk factors, such as insulin resistance and hypertension, adipocytokines released from perirenal adipose tissue (PRAT) may be involved in pathogenesis of MetS nephropathy.…”