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Human coronary artery perivascular adipocytes overexpress genes responsible for regulating vascular morphology, inflammation, and hemostasis.

ABSTRACT: Inflammatory cross talk between perivascular adipose tissue and the blood vessel wall has been proposed to contribute to the pathogenesis of atherosclerosis. We previously reported that human perivascular (PV) adipocytes exhibit a proinflammatory phenotype and less adipogenic differentiation than do subcutaneous (SQ) adipocytes. To gain a global view of the genomic basis of biologic differences between PV and SQ adipocytes, we performed genome-wide expression analyses to identify differentially expressed genes between adipocytes derived from human SQ vs. PV adipose tissues. Although >90% of well-expressed genes were similarly regulated, we identified a signature of 307 differentially expressed genes that were highly enriched for functions associated with the regulation of angiogenesis, vascular morphology, inflammation, and blood clotting. Of the 156 PV upregulated genes, 59 associate with angiogenesis, vascular biology, or inflammation, noteworthy of which include TNFRSF11B (osteoprotegerin), PLAT, TGFB1, THBS2, HIF1A, GATA6, and SERPINE1. Of 166 PV downregulated genes, 21 associated with vascular biology and inflammation, including ANGPT1, ANGPTL1, and VEGFC. Consistent with the emergent hypothesis that PV adipocytes differentially regulate angiogenesis and inflammation, cell culture-derived adipocyte-conditioned media from PV adipocytes strongly enhanced endothelial cell tubulogenesis and monocyte migration compared with media from SQ adipocytes. These findings demonstrate that PV adipocytes have the potential to significantly modulate vascular inflammatory crosstalk in the setting of atherosclerosis by their ability to signal to both endothelial and inflammatory cells.

SUBMITTER: Chatterjee TK

PROVIDER: S-EPMC3742916 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Human coronary artery perivascular adipocytes overexpress genes responsible for regulating vascular morphology, inflammation, and hemostasis.

Chatterjee Tapan K TK Aronow Bruce J BJ Tong Wilson S WS Manka David D Tang Yaoliang Y Bogdanov Vladimir Y VY Unruh Dusten D Blomkalns Andra L AL Piegore Mark G MG Weintraub Daniel S DS Rudich Steven M SM Kuhel David G DG Hui David Y DY Weintraub Neal L NL

Physiological genomics 20130604 16

Inflammatory cross talk between perivascular adipose tissue and the blood vessel wall has been proposed to contribute to the pathogenesis of atherosclerosis. We previously reported that human perivascular (PV) adipocytes exhibit a proinflammatory phenotype and less adipogenic differentiation than do subcutaneous (SQ) adipocytes. To gain a global view of the genomic basis of biologic differences between PV and SQ adipocytes, we performed genome-wide expression analyses to identify differentially ...[more]

PMID: 23737535

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Project description:Objective- Perivascular adipose tissue (PVAT) contains an independent adrenergic system that can take up, metabolize, release, and potentially synthesize the vasoactive catecholamine norepinephrine. Norepinephrine has been detected in PVAT, but the mechanism of its protection within this tissue is unknown. Here, we investigate whether PVAT adipocytes can store norepinephrine using VMAT (vesicular monoamine transporter). Approach and Results- High-performance liquid chromatography identified norepinephrine in normal male Sprague Dawley rat aortic, superior mesenteric artery, and mesenteric resistance vessel PVATs, and retroperitoneal fat. Real-time polymerase chain reaction revealed VMAT1 and VMAT2 mRNA expression in the adipocytes and stromal vascular fraction of mesenteric resistance vessel PVAT. Immunofluorescence demonstrated the presence of VMAT1 and VMAT2, and the colocalization of VMAT2 with norepinephrine, in the cytoplasm of adipocytes in mesenteric resistance vessel PVAT. A protocol was developed to capture real-time uptake of Mini 202-a functional and fluorescent VMAT probe-in live rat PVAT adipocytes. Mini 202 was taken up by freshly isolated and differentiated adipocytes from mesenteric resistance vessel PVAT and adipocytes from thoracic aortic and superior mesenteric artery PVATs. In adipocytes freshly isolated from mesenteric resistance vessel PVAT, addition of rose bengal (VMAT inhibitor), nisoxetine (norepinephrine transporter inhibitor), or corticosterone (organic cation 3 transporter inhibitor) significantly reduced Mini 202 signal. Immunofluorescence supports that neither VMAT1 nor VMAT2 is present in retroperitoneal adipocytes, suggesting that PVAT adipocytes may be unique in storing norepinephrine. Conclusions- This study supports a novel function of PVAT adipocytes in storing amines in a VMAT-dependent manner. It provides a foundation for future studies exploring the purpose and mechanisms of norepinephrine storage by PVAT in normal physiology and obesity-related hypertension.

Project description:Purpose To evaluate the frequency and implications of perivascular fat stranding on coronary computed tomography (CT) angiograms obtained for suspected acute coronary syndrome (ACS). Materials and Methods This retrospective registry study was approved by the institutional review board. The authors reviewed the medical records and images of 1403 consecutive patients (796 men, 607 women; mean age, 52.8 years) who underwent coronary CT angiography at the emergency department from February 2012 to March 2016. Fat attenuation, length and number of circumferential quadrants of the affected segment, and attenuation values in the unaffected epicardial and subcutaneous fat were measured. "Cases" were defined as patients with perivascular fat stranding. Patients with significant stenosis but without fat stranding were considered control subjects. Baseline imaging characteristics, ACS frequency, and results of subsequent downstream testing were compared between cases and control subjects by using two-sample t, Mann-Whitney U, and Fisher tests. Results Perivascular fat stranding was seen in 11 subjects, nine with atherosclerotic lesions and two with spontaneous coronary artery dissections, with a mean fat stranding length of 19.2 mm and circumferential extent averaging 2.9 quadrants. The mean attenuation of perivascular fat stranding, normal epicardial fat, and normal subcutaneous fat was 17, -93.2, and -109.3 HU, respectively (P < .001). Significant differences (P < .05) between cases and control subjects included lower Agatston score, presence of wall motion abnormality, and initial elevation of serum troponin level. ACS frequency was 45.4% in cases and 3.8% in control subjects (P = .001). Conclusion Recognition of perivascular fat stranding may be a helpful additional predictor of culprit lesion and marker of risk for ACS in patients with significant stenosis or spontaneous coronary artery dissection. © RSNA, 2018 Online supplemental material is available for this article.

Project description:Background Perivascular adipose tissue (PVAT) is associated with metabolically driven chronic inflammation called metaflammation, which contributes to vascular function and the pathogenesis of vascular disease. The saphenous vein (SV) is commonly used as an essential conduit in coronary artery bypass grafting, but the long-term patency of SV grafts is a crucial issue. The use of the novel "no-touch" technique of SV harvesting together with its surrounding tissue has been reported to result in good long‑term graft patency of SV grafts. Herein, we investigated whether PVAT surrounding the SV (SV-PVAT) has distinct phenotypes compared with other PVATs of vessels. Methods and Results Fat pads were sampled from 48 patients (male/female, 32/16; age, 72±8 years) with coronary artery disease who underwent elective coronary artery bypass grafting. Adipocyte size in SV-PVAT was significantly larger than the sizes in PVATs surrounding the internal thoracic artery, coronary artery, and aorta. SV-PVAT and PVAT surrounding the internal thoracic artery had smaller extents of fibrosis, decreased gene expression levels of fibrosis-related markers, and less metaflammation, as indicated by a significantly smaller extent of cluster of differentiation 11c-positive M1 macrophage infiltration, higher gene expression level of adiponectin, and lower gene expression levels of inflammatory cytokines, than did PVATs surrounding the coronary artery and aorta. Expression patterns of adipocyte developmental and pattern-forming genes were totally different among the PVATs of the vessels. Conclusions The phenotype of SV-PVAT, which may result from inherent differences in adipocytes, is closer to that of PVAT surrounding the internal thoracic artery than that of PVAT surrounding the coronary artery or that of PVAT surrounding the aorta. SV-PVAT has less metaflammation and consecutive adipose tissue remodeling, which may contribute to high long-term patency of grafting when the no-touch technique of SV harvesting is used.

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Human coronary artery perivascular adipocytes overexpress genes responsible for regulating vascular morphology, inflammation, and hemostasis.

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Human coronary artery perivascular adipocytes overexpress genes responsible for regulating vascular morphology, inflammation, and hemostasis.

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