UNASSIGNED: Magnetic resonance imaging (MRI) has the potential in assessing the inflammation of perivascular adipose tissue (PVAT) due to its excellent soft tissue contrast. However, evidence is lacking for the association between carotid PVAT measured by MRI and carotid vulnerable atherosclerotic plaques. This study aimed to investigate the association between signal intensity of PVAT and vulnerable plaques in carotid arteries using multi-contrast magnetic resonance (MR) vessel wall imaging.
UNASSIGNED: In this cross-sectional study, a total of 104 patients (mean age, 64.9±7.0 years; 86 men) with unilateral moderate-to-severe atherosclerotic stenosis referred to carotid endarterectomy (CEA) were recruited from April 2018 to December 2020 at Department of Neurosurgery of Peking University Third Hospital. All patients underwent multi-contrast MR vessel wall imaging including time-of-flight (ToF) MR angiography, black-blood T1-weighted (T1w) and T2-weighted (T2w) and simultaneous non-contrast angiography and intraplaque hemorrhage (IPH) imaging sequences. Patients with contraindications to endarterectomy or MRI examinations were excluded. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of PVAT were measured on ToF images and vulnerable plaque characteristics including IPH, large lipid-rich necrotic core (LRNC), and fibrous cap rupture (FCR) were identified. The SNR and CNR of PVAT were compared between slices with and without vulnerable plaque features using Mann-Whitney U test and their associations were analyzed using the generalized linear mixed model (GLMM).
UNASSIGNED: Carotid artery slices with IPH (30.93±14.56 vs. 27.34±10.02; P<0.001), FCR (30.35±13.82 vs. 27.53±10.37; P=0.006), and vulnerable plaque (29.15±12.52 vs. 27.32±10.05; P=0.016) had significantly higher value of SNR of PVAT compared to those without. After adjusting for clinical confounders, the SNR of PVAT was significantly associated with presence of IPH [odds ratio (OR) =0.627, 95% confidence interval (CI): 0.465-0.847, Puncorr=0.002, PFDR=0.016] and vulnerable plaque (OR =0.762, 95% CI: 0.629-0.924, Puncorr=0.006, PFDR=0.020). However, no significant association was found between the CNR of PVAT and presence of vulnerable plaque features (all P>0.05).
UNASSIGNED: The SNR of carotid artery PVAT measured by ToF MR angiography is independently associated with vulnerable atherosclerotic plaque features, suggesting that the signal intensity of PVAT might be an effective indicator for vulnerable plaque.

Perivascular adipose tissue (PVAT), a fat layer that provides structural support to the blood vessels, is a cushion protecting the vessel wall from neighbouring tissues during contraction and relaxation. PVAT actively regulates vascular tone by secreting vasoactive (vasodilatory and vasoconstrictive) factors (e.g., adipokines, batokines, and lipokines) or microRNA (miRNA)-containing exosomes to reduce the hyperreactivity induced by obesity. Of particular interest are adipocyte-derived exosomal miRNAs, which act as crucial regulators, counteracting the detrimental effects of obesity on cardiovascular well-being. These exosomes serve as potent messengers, facilitating the transport of miRNAs and other bioactive molecules involved in intercellular communication. Undoubtedly, the unique function of exosomal miRNAs promotes vascular homeostasis by fine-tuning endothelial function, vascular remodelling, and inflammatory environment, thereby preventing cardiovascular disease. The collective findings comprehensively explain their protective functions by exploring the intricate mechanisms through which PVAT and adipocyte-derived exosomal miRNAs collaboratively orchestrate vascular health. Taken together, this review strategically focuses on PVAT, exosomes, and adipocyte-derived miRNAs, offering valuable insights that can potentially inform the development of targeted interventions for cardiovascular diseases.

Cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2DM) are two of the four major chronic non-communicable diseases (NCDs) representing the leading cause of death worldwide. Several studies demonstrate that endothelial dysfunction (ED) plays a central role in the pathogenesis of these chronic diseases. Although it is well known that systemic chronic inflammation and oxidative stress are primarily involved in the development of ED, recent studies have shown that perivascular adipose tissue (PVAT) is implicated in its pathogenesis, also contributing to the progression of atherosclerosis and to insulin resistance (IR). In this review, we describe the relationship between PVAT and ED, and we also analyse the role of PVAT in the pathogenesis of CVDs and T2DM, further assessing its potential therapeutic target with the aim of restoring normal ED and reducing global cardiovascular risk.

Perivascular adipose tissue and the vessel wall are connected through intricate bidirectional paracrine and vascular secretory signaling pathways. The secretion of inflammatory factors and oxidative products by the vessel wall in the diseased segment has the ability to influence the phenotype of perivascular adipocytes. Additionally, the secretion of adipokines by perivascular adipose tissue exacerbates the inflammatory response in the diseased vessel wall. Therefore, quantitative and qualitative studies of perivascular adipose tissue are of great value in the context of vascular inflammation and may provide a reference for the assessment of cardiovascular ischemic disease.

UNASSIGNED: Extracranial atherosclerosis is one of the major causes of stroke. Carotid computed tomography angiography (CTA) is a widely used imaging modality that allows detailed assessments of plaque characteristics. This study aimed to develop and test radiomics models of carotid plaques and perivascular adipose tissue (PVAT) to distinguish symptomatic from asymptomatic plaques and compare the diagnostic value between radiomics models and traditional CTA model.
UNASSIGNED: A total of 144 patients with carotid plaques were divided into symptomatic and asymptomatic groups. The traditional CTA model was built by the traditional radiological features of carotid plaques measured on CTA images which were screened by univariate analysis and multivariable logistic regression. We extracted and screened radiomics features from carotid plaques and PVAT. Then, a support vector machine was used for building plaque and PVAT radiomics models, as well as a combined model using traditional CTA features and radiomics features. The diagnostic value between radiomics models and traditional CTA model was compared in identifying symptomatic carotid plaques by Delong method.
UNASSIGNED: The area under curve (AUC) values of traditional CTA model were 0.624 and 0.624 for the training and validation groups, respectively. The plaque radiomics model and PVAT radiomics model achieved AUC values of 0.766, 0.740 and 0.759, 0.618 in the two groups, respectively. Meanwhile, the combined model of plaque and PVAT radiomics features and traditional CTA features had AUC values of 0.883 and 0.840 for the training and validation groups, respectively, and the receiver operating characteristic curves of combined model were significantly better than those of traditional CTA model in the training group (P<0.001) and validation group (P=0.029).
UNASSIGNED: The combined model of the radiomics features of carotid plaques and PVAT and the traditional CTA features significantly contributes to identifying high-risk carotid plaques compared with traditional CTA model.

During hypertension, vascular remodeling allows the blood vessel to withstand mechanical forces induced by high blood pressure (BP). This process is well characterized in the media and intima layers of the vessel but not in the perivascular adipose tissue (PVAT). In PVAT, there is evidence for fibrosis development during hypertension; however, PVAT remodeling is poorly understood. In non-PVAT depots, mechanical forces can affect adipogenesis and lipogenic stages in preadipocytes. In tissues exposed to high magnitudes of pressure like bone, the activation of the mechanosensor PIEZO1 induces differentiation of progenitor cells towards osteogenic lineages. PVAT\'s anatomical location continuously exposes it to forces generated by blood flow that could affect adipogenesis in normotensive and hypertensive states. In this study, we hypothesize that activation of PIEZO1 reduces adipogenesis in PVAT preadipocytes. The hypothesis was tested using pharmacological and mechanical activation of PIEZO1. Thoracic aorta PVAT (APVAT) was collected from 10-wk old male SD rats (n=15) to harvest preadipocytes that were differentiated to adipocytes in the presence of the PIEZO1 agonist Yoda1 (10 µM). Mechanical stretch was applied with the FlexCell System at 12% elongation, half-sine at 1 Hz simultaneously during the 4 d of adipogenesis (MS+, mechanical force applied; MS-, no mechanical force used). Yoda1 reduced adipogenesis by 33% compared with CON and, as expected, increased cytoplasmic Ca2+ flux. MS+ reduced adipogenesis efficiency compared with MS-. When Piezo1 expression was blocked with siRNA [siPiezo1; NC=non-coding siRNA], the anti-adipogenic effect of Yoda1 was reversed in siPiezo1 cells but not in NC; in contrast, siPiezo1 did not alter the inhibitory effect of MS+ on adipogenesis. These data demonstrate that PIEZO1 activation in PVAT reduces adipogenesis and lipogenesis and provides initial evidence for an adaptive response to excessive mechanical forces in PVAT during hypertension.

UNASSIGNED: To investigate the association between the perivascular adipose tissue (PVAT) fat attenuation index (FAI) derived from coronary computed tomography angiography (CCTA) and the prevalence of in-stent restenosis (ISR) in patients with coronary stent implantation.
UNASSIGNED: A total of 117 patients with previous coronary stenting referred for invasive coronary angiography (ICA) were enrolled in this retrospective observational analysis. All patients underwent CCTA between July 2016 and November 2021. The deep learning-based (DL-based) method was used to analyze and measure the peri-stent FAI value. Additionally, the relationship between hematological and biochemical parameters collected from all the patients was also explored. The least absolute shrinkage and selection operator (LASSO) method was applied to the most useful feature selection, and binary logistic regression was used to test the association between the selected features and ISR. The predictive performance for ISR of the identified subgroups was evaluated by calculating the area under the curve (AUC) of receiver operator curves plotted for each model. The Pearson correlation coefficient was used to assess the correlation of peri-stent FAI values with degrees of ISR.
UNASSIGNED: The peri-stent FAI values in the ISR group were significantly higher than those in the non-ISR group (-78.1 ± 6.2 HU vs. -87.2 ± 7.3 HU, p < 0.001). The predictive ISR features based on the LASSO analysis were peri-stent FAI, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (ApoA1), and high-sensitivity c-reactive protein (hs-CRP), with an AUC of 0.849, 0.632, 0.620, and 0.569, respectively. Binary logistic regression analysis determined that peri-stent FAI was uniquely and independently associated with ISR after adjusting for other risk factors (odds ratio [OR] 1.403; 95% CI: 1.211 to 1.625; p < 0.001). In the subgroup analysis, the AUCs of the left anterior descending coronary artery (LAD), left circumflex coronary artery (LCx), and right coronary artery (RCA) stents groups were 0.80, 0.87, and 0.96, respectively. The Pearson\'s correlation coefficient indicated a term moderately correlation between ISR severity and peri-stent FAI values (r = 0.579, P < 0.001).
UNASSIGNED: The peri-stent FAI can be used as an independently non-invasive biomarker to predict ISR risk and severity after stent implantation.

High-fat diet (HFD)-induced vascular impairment in mice is associated with a dysfunction of the perivascular adipose tissue (PVAT). The present study was conducted to investigate the involvement of sirtuin 1 (SIRT1). Male C57BL/6J mice were fed an HFD for 20 weeks to induce obesity. Vascular function was analyzed using a wire myograph system. In obese mice, the vasodilator response of PVAT-containing aortas to acetylcholine was reduced, although the vascular function of PVAT-free aortas remained normal. SIRT1 activity in PVAT of obese mice was reduced despite enhanced SIRT1 expression. Nicotinamide adenine dinucleotide (NAD+) levels and the NAD+/NADH ratio in the PVAT of obese mice were decreased, which was likely attributable to a downregulation of the NAD+-producing enzyme NAMPT. The reduced SIRT1 activity was associated with an enhanced acetylation of the endothelial nitric oxide synthase (eNOS) in the PVAT. Ex vivo incubation of PVAT-containing aorta from obese mice with NAD+ led to a complete normalization of vascular function. Thus, reduced SIRT1 activity due to NAD+ deficiency is involved in obesity-induced PVAT dysfunction.

Background: Perivascular adipose tissue (PVAT) imaging can be used in clinical practice as a surrogate marker of vascular disease. We aimed to analyze the association between the density of carotid artery PVAT and clinical features and outcomes in stroke patients treated with mechanical thrombectomy. Methods: A total of 183 consecutive patients treated with mechanical thrombectomy due to anterior circulation large vessel occlusion were retrospectively included from January 2016 to May 2021. The density of carotid artery PVAT was evaluated by preoperative computed tomography angiography. Successful arterial recanalization was defined as a modified Thrombolysis in Cerebral Infarction score of 2b-3 on the final angiographic examination. Poor functional outcome was defined as a modified Rankin Scale (mRS) score > 2 at 3 months after stroke. We assessed the independent effect of carotid artery PVAT density on revascularization, functional outcome, and mortality using logistic regression models adjusted for relevant confounders. Results: Patients with large artery atherosclerotic stroke have higher carotid artery PVAT density than patients with other stroke etiologies (-65.82 ± 12.96 vs. -75.77 ± 13.44, P < 0.001). Higher carotid artery PVAT density was associated with unsuccessful recanalization [adjusted odds ratio (AOR) (95% CI), 2.968 (1.292, 6.819), P = 0.010], and poor outcome [AOR (95% CI), 2.704 (1.610, 4.541), P < 0.001] and mortality [AOR (95% CI), 1.894 (1.040, 3.449), P = 0.037] at 3 months in stroke patients treated with thrombectomy. Conclusion: Higher carotid artery PVAT density before mechanical thrombectomy is an indicator of worse postprocedural arterial revascularization and a worse functional outcome in acute stroke patients.

Trimethylamine (TMA), formed by intestinal microbiota, and its Flavin-Monooxygenase 3 (FMO3) product Trimethylamine-N-Oxide (TMAO), are potential modulators of host cardiometabolic phenotypes. High circulating levels of TMAO are associated with increased risk for cardiovascular diseases. We hypothesized that TMA/TMAO could directly change the vascular tone. Perivascular adipose tissue (PVAT) helps to regulate vascular homeostasis and may also possess FMO3. Thoracic aorta with(+) or without(-) PVAT, also + or - the endothelium (E), of male Sprague Dawley rats were isolated for measurement of isometric tone in response to TMA/TMAO (1nM-0.5 M). Immunohistochemistry (IHC) studies were done to identify the presence of FMO3. TMA and TMAO elicited concentration-dependent arterial contraction. However, at a maximally achievable concentration (0.2 M), contraction stimulated by TMA was of a greater magnitude (141.5 ± 16% of maximum phenylephrine contraction) than that elicited by TMAO (19.1 ± 4.03%) with PVAT and endothelium intact. When PVAT was preserved, TMAO-induced contraction was extensively reduced the presence (19.1 ± 4.03%) versus absence of E (147.2 ± 20.5%), indicating that the endothelium plays a protective role against TMAO-induced contraction. FMO3 enzyme was present in aortic PVAT, but the FMO3 inhibitor methimazole did not affect contraction stimulated by TMA in aorta + PVAT. However, the l-type calcium channel blocker nifedipine reduced TMA-induced contraction by ∼50% compared to the vehicle. Though a high concentration of these compounds was needed to achieve contraction, the findings that TMA-induced contraction was independent of PVAT and E and mediated by nifedipine-sensitive calcium channels suggest metabolite-induced contraction may be physiologically important.