a Department of Medicine (Cardiology) , University of British Columbia , Vancouver , BC , Canada.
Clin Exp Hypertens. 2018;40(2):155-166. doi: 10.1080/10641963.2017.1346113. Epub 2017 Nov 15.
Gene expression and associations were examined in a model of heart failure with preserved ejection fraction (HFpEF), a condition with minimal effective treatment. Genes with at least two studies showing significant changes in Dahl rat with heart failure were examined by meta-analysis. Significantly increased in expression were iNOS, p47phox, ADM, ANP, OPN, ACE, MCP-1, GP91PHOX, ICAM-1, TGF-β1, CTGF, ET-1, p22phox, ETB, BNP, ETA, MMP13, Col1a1, MMP2, TIMP1, Col3a1, Il-1β, β-MHC, ECE1, MMP14, AGT, and MMP9. In contrast, GLUT4, VEGF, eNOS, HIF-1α, and PGC1-α were significantly decreased in expression. The top biological process clusters identified in Database for Annotation, Visualization and Integrated Discovery, ToppGene, and PANTHER were collagen metabolic process, cellular ion homeostasis, regulation of cell migration, and response to decreased oxygen levels. These data suggest refocusing understanding of the pathophysiology of HFpEF to pathways involved in collagen metabolism, cell migration likely for inflammatory cells, and responses to decreased oxygen levels. Abbreviations Inducible nitric oxide synthase (INOS), neutrophil cytosolic factor 1 (p47phox), adrenomedullin (ADM), atrial natriuretic peptide (ANP), osteopontin (OPN/SPP1), angiotensin converting enzyme (ACE), monocyte chemotactic protein 1 (MCP-1), cytochrome b-245 beta polypeptide (gp91phox), intercellular adhesion molecule 1 (ICAM-1), transforming growth factor beta 1 (TGF-β1), connective tissue growth factor (CTGF), endothelin-1 (ET-1), cytochrome B-245, alpha polypeptide (p22phox), endothelin receptor type B (ETB/EDNRB), brain natriuretic peptide (BNP), endothelin receptor type A (ETA/EDNRA), matrix metallopeptidase 13 (MMP13), type I collagen (Col1a1), matrix metallopeptidase 2 (MMP2), TIMP metallopeptidase inhibitor 1 (TIMP1), Type III collagen (Col3a1), interleukin 1 beta (IL-1β), beta myocin heavy chain (β-MHC), endothelin converting enzyme 1 (ECE1) matrix metallopeptidase 14 (MMP14), angiotensinogen (AGT), angiotensin II receptor Type 1 (AT1R), cytochrome C oxidase I (COX1), fms-like tyrosine kinase 1 (FLT1), TIMP metallopeptidase inhibitor 2 (TIMP2), phospholamban (PLN), vascular cell adhesion molecule 1 (VCAM1), extracellular matrix (ECM).
基因表达和相关性在射血分数保留心力衰竭（HFpEF）模型中进行了研究，HFpEF 是一种治疗效果极小的病症。通过荟萃分析检查了至少有两项研究表明在心力衰竭的 Dahl 大鼠中发生显著变化的基因。iNOS、p47phox、ADM、ANP、OPN、ACE、MCP-1、GP91PHOX、ICAM-1、TGF-β1、CTGF、ET-1、p22phox、ETB、BNP、ETA、MMP13、Col1a1、MMP2、TIMP1、Col3a1、IL-1β、β-MHC、ECE1、MMP14、AGT 和 MMP9 的表达显著增加。相比之下，GLUT4、VEGF、eNOS、HIF-1α 和 PGC1-α 的表达显著降低。在数据库中的注释、可视化和综合发现、ToppGene 和 PANTHER 中鉴定的顶级生物学过程聚类是胶原代谢过程、细胞离子稳态、细胞迁移调节和对低氧水平的反应。这些数据表明，重新关注 HFpEF 病理生理学的理解，以涉及胶原代谢、细胞迁移（可能是炎症细胞）和对低氧水平反应的途径为目标。
缩写词 诱导型一氧化氮合酶（INOS）、中性粒细胞胞质因子 1（p47phox）、肾上腺髓质素（ADM）、心房利钠肽（ANP）、骨桥蛋白（OPN/SPP1）、血管紧张素转换酶（ACE）、单核细胞趋化蛋白 1（MCP-1）、细胞色素 b-245 beta 多肽（gp91phox）、细胞间黏附分子 1（ICAM-1）、转化生长因子β 1（TGF-β1）、结缔组织生长因子（CTGF）、内皮素-1（ET-1）、细胞色素 B-245，alpha 多肽（p22phox）、内皮素受体 B（ETB/EDNRB）、脑利钠肽（BNP）、内皮素受体 A（ETA/EDNRA）、基质金属蛋白酶 13（MMP13）、I 型胶原（Col1a1）、基质金属蛋白酶 2（MMP2）、TIMP 金属蛋白酶抑制剂 1（TIMP1）、III 型胶原（Col3a1）、白细胞介素 1β（IL-1β）、β-肌球蛋白重链（β-MHC）、内皮素转化酶 1（ECE1）基质金属蛋白酶 14（MMP14）、血管紧张素原（AGT）、血管紧张素 II 受体 1（AT1R）、细胞色素 C 氧化酶 I（COX1）、fms 样酪氨酸激酶 1（FLT1）、TIMP 金属蛋白酶抑制剂 2（TIMP2）、磷蛋白（PLN）、血管细胞黏附分子 1（VCAM1）、细胞外基质（ECM）。
