Key result
In aged ApoE-/- rats, maximal endothelium-dependent relaxation without PVAT was severely impaired vs controls (p=0.012), but PVAT compensated for this dysfunction by contributing nitric oxide.
Why the study?
Atherosclerosis is accompanied by vascular inflammation and endothelial dysfunction, but the role of perivascular adipose tissue in modulating vascular relaxation in early atherosclerosis remained to be investigated.
In a rat model of early atherosclerosis, inflammatory perivascular adipose tissue compensates for severe endothelial dysfunction by contributing nitric oxide upon cholinergic stimulation.
Answers are grounded in this paper and cite their sources.
PVAT modulation of aortic relaxation in early atherosclerosis is hypothesis-generating; leaves open translational relevance to human endothelial dysfunction.
Atherosclerosis is a major contributor to global mortality and is accompanied by vascular inflammation and endothelial dysfunction. Perivascular adipose tissue (PVAT) is an established regulator of vascular function with emerging implications in atherosclerosis. We investigated the modulation of aortic relaxation by PVAT in aged rats with apolipoprotein E deficiency (ApoE−/−) fed a high-fat diet as a model of early atherosclerosis. ApoE−/− rats (N = 7) and wild-type Sprague-Dawley controls (ApoE+/+, N = 8) received high-fat diet for 51 weeks. Hyperlipidemia was confirmed in ApoE−/− rats by elevated plasma cholesterol (p < 0.001) and triglyceride (p = 0.025) levels. Early atherosclerosis was supported by increased intima/media thickness ratio (p < 0.01) and ED1-positive macrophage influx in ApoE−/− aortic intima (p < 0.001). Inflammation in ApoE−/− PVAT was characteristic by an increased [18F]FDG uptake (p < 0.01), ED1-positive macrophage influx (p = 0.0003), mRNA expression levels of CD68 (p < 0.001) and IL-1β (p < 0.01), and upregulated iNOS protein (p = 0.011). The mRNAs of MCP-1, IL-6 and adiponectin remained unchanged in PVAT. Aortic PVAT volume measured with micro-PET/CT was increased in ApoE−/− rats (p < 0.01). Maximal endothelium-dependent relaxation (EDR) to acetylcholine in ApoE−/− aortic rings without PVAT was severely impaired (p = 0.012) compared with controls, while ApoE−/− aortic rings with PVAT showed higher EDR than controls. All EDR responses were blocked by L-NMMA and the expression of eNOS mRNA was increased in ApoE−/− PVAT (p = 0.035). Using a rat ApoE−/− model of early atherosclerosis, we capture a novel mechanism by which inflammatory PVAT compensates severe endothelial dysfunction by contributing NO upon cholinergic stimulation.
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Nakládal et al. (2021) studied Early atherosclerosis (n=15). ApoE deficiency and high-fat diet vs. Wild-type controls was evaluated on Maximal endothelium-dependent relaxation (EDR) to acetylcholine (p=0.012). In aged ApoE-/- rats, maximal endothelium-dependent relaxation without PVAT was severely impaired vs controls (p=0.012), but PVAT compensated for this dysfunction by contributing nitric oxide.
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