Ellis Caitlin P S, Tero Benjamin W, Potts Christian M, Malka Kimberly T, Yang Xuehui, Hamilton Joshua, Vary Calvin, Khalil Andre, Liaw Lucy
MaineHealth Institute for Research, Scarborough, ME 04074, USA.
Graduate School of Biomedical Science and Engineering, University of Maine, Orono, ME 04469, USA.
Biomedicines. 2024 Oct 25;12(11):2453. doi: 10.3390/biomedicines12112453.
: Perivascular adipose tissue (PVAT) exerts a paracrine effect on blood vessels and our objective was to understand PVAT molecular signatures related to cardiovascular disease. : We studied two groups: those undergoing mitral valve repair/replacement (VR, n = 16) and coronary artery bypass graft (CABG, n = 38). VR donors did not have coronary artery disease, whereas CABG donors had advanced coronary artery disease. Clinical and tissue pathologies and proteomics from adipose tissue were assessed. : Donors undergoing VR had a lower body mass index ( = 0.01), HbA1C ( = 0.0023), and incidence of diabetes ( = 0.022) compared to CABG. VR donors were overall healthier, with higher cardiac function compared to CABG donors, based on ejection fraction. Although adipose histopathology between groups was not markedly different, PVAT had smaller and more adipocytes compared to subcutaneous adipose tissues. These differences were validated by whole specimen automated morphological analysis, and anisotropy analysis showed small (2.8-7.5 μm) and large (22.8-64.4 μm) scale differences between perivascular and subcutaneous adipose tissue from CABG donors, and small scale changes (2.8-7.5 μm) between perivascular and subcutaneous adipose tissue from VR donors. Distinct protein signatures in PVAT and subcutaneous adipose tissue include those involved in secretion, exosomes and vesicles, insulin resistance, and adipocyte identity. Comparing PVAT and subcutaneous adipose tissue from CABG donors, there were 82 significantly different proteins identified with log fold change ≥ 0.3 or ≤-0.3 ( < 0.05). Using this threshold, there were 36 differences when comparing PVAT and subcutaneous adipose tissue from VR donors, 58 differences when comparing PVAT from CABG or VR donors, and 55 when comparing subcutaneous adipose tissue from CABG vs. VR donors. : Routine histopathology cannot differentiate between PVAT from donors with or without coronary artery disease, but multiscale anisotropy analysis discriminated between these populations. Our mass spectrometry analysis identified a cohort of proteins that distinguish between adipose depots, and are also associated with the presence or absence of coronary artery disease.
血管周围脂肪组织（PVAT）对血管具有旁分泌作用，我们的目标是了解与心血管疾病相关的PVAT分子特征。我们研究了两组：接受二尖瓣修复/置换术的患者（VR，n = 16）和冠状动脉旁路移植术的患者（CABG，n = 38）。VR组的供体没有冠状动脉疾病，而CABG组的供体患有晚期冠状动脉疾病。对临床和组织病理学以及脂肪组织的蛋白质组学进行了评估。与CABG组相比，接受VR手术的供体体重指数更低（P = 0.01）、糖化血红蛋白水平更低（P = 0.0023）、糖尿病发病率更低（P = 0.022）。基于射血分数，VR组供体总体上更健康，心脏功能比CABG组供体更高。尽管两组之间的脂肪组织病理学没有明显差异，但与皮下脂肪组织相比，PVAT的脂肪细胞更小且更多。这些差异通过全标本自动形态分析得到验证，各向异性分析显示CABG组供体的血管周围脂肪组织和皮下脂肪组织之间存在小尺度（2.8 - 7.5μm）和大尺度（22.8 - 64.4μm）差异，VR组供体的血管周围脂肪组织和皮下脂肪组织之间存在小尺度变化（2.8 - 7.5μm）。PVAT和皮下脂肪组织中不同的蛋白质特征包括参与分泌、外泌体和囊泡、胰岛素抵抗以及脂肪细胞特性的那些蛋白质。比较CABG组供体的PVAT和皮下脂肪组织，发现82种蛋白质有显著差异，其对数倍变化≥0.3或≤ - 0.3（P < 0.05）。使用这个阈值，比较VR组供体的PVAT和皮下脂肪组织时有36个差异，比较CABG组或VR组供体的PVAT时有58个差异，比较CABG组和VR组供体的皮下脂肪组织时有55个差异。常规组织病理学无法区分有无冠状动脉疾病的供体的PVAT，但多尺度各向异性分析可以区分这些人群。我们的质谱分析确定了一组能够区分脂肪储存部位且与冠状动脉疾病存在与否相关的蛋白质。
