Abstract 14169: Latent Transforming Growth Factor-Beta-Binding Protein 4 Deficiency Attenuated Renal Fibrosis After Myocardial Infarction

• Published in: Circulation (New York, N.Y.) N.Y.), 2019-11, Vol.140 (Suppl_1 Suppl 1), p.A14169-A14169
• Main Authors: Su, Chi-Ting, Fang, I-Hsien, Liu, Yen-wen, Jao, Tzu-Ming, Urban, Zsolt
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.140.suppl_1.14169

IntroductionAfter myocardial infarction (MI), renal injury is common and a predictor for poor prognosis. The cross-talk between heart and kidney is complex. Transforming growth factor beta (TGF) is a key cytokine that promotes cardiac and renal fibrosis. Latent transforming growth factor-beta-binding proteins (LTBPs) regulate TGF signaling and activation. Therefore, we investigated the pathophysiological role of LTBP4 in renal impairment after myocardial infarction.HypothesisLTBP4 contributes to renal fibrosis after myocardial infarction.MethodsUnilateral nephrectomy was performed one week before inducing myocardial infarction by ligation of the left anterior descending artery in wild-type (WT) and Ltbp4S-/- mice. Sham surgery was performed on control animals. Echocardiogarphy and picrosirius red/fast green-stained histology studies were used to demonstrate the cardiac dysfunction after myocardial infarction. Renal tissues were collected for histology, protein and gene studies at 1, 2, 4, 8, 10, 12 weeks after the surgery. Serum studies for renal functions and urine studies for albumin level were documented in serious.ResultsAfter myocardial infarction, echocardiography demonstrated systolic dysfunction with anterior wall hypokinesia and histology studies revealed obvious cardiac fibrosis. In renal tissues, interleukin 6 (IL- 6) and monocyte chemoattractant protein-1(MCP-1) were significantly up-regulated in MI animals two weeks earlier than in controls. Moreover, 10 weeks after MI surgery, picrosirius red staining revealed renal interstitial fibrosis but the severity was weaker in Ltbp4S-/- mice, compared with WT mice. Enhanced expressions of kidney injury molecule-1 (KIM1), LTBP4 and TGFβ and platelet derived growth factor receptor beta (PDGFRB) were elevated in MI animals compared to sham, but the degree of up-regulation was more prominent in WT than in Ltbp4S-/- mice.ConclusionsCardiac fibrosis can enhance renal inflammation and exacerbate renal fibrosis. Inflammation preceded the expression of fibrotic factors. LTBP4 enhances TGFβ signaling and may be a therapeutic target to mitigate post-MI renal injury.