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J Clin Med. 2019;8(3):jcm8030366.

Fimasartan for Remodeling after Myocardial Infarction.

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제1저자 임병관 박진주 · 교신저자 최동주

PMID 30875971 PMC6463200 DOI 10.3390/jcm8030366 IF 3.3 순환기내과
소속 (7)
  1. Department of Biomedical Science, Jungwon University, Goesan-gun 28024, Korea. bkwan.lim@gmail.com.
  2. Department of Internal Medicine, College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea. jinjooparkmd@gmail.com.
  3. Division of Cardiology, Department of Internal Medicine, Cardiovascular Imaging Center, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea. tyche.park@gmail.com.
  4. Division of Cardiology, Department of Internal Medicine, Cardiovascular Imaging Center, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea. eelulee@daum.net.
  5. Division of Cardiovascular and Rare Disease, Korea National Institute of Health, Osong, Cheongju, Chungbuk 28159, Korea. gonkjs@hanmail.net.
  6. Department of Internal Medicine, College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea. until10@hanmail.net.
  7. Department of Internal Medicine, College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea. djchoi@snubh.org.

Abstract

An angiotensin receptor blocker (ARB) mitigates cardiac remodeling after myocardial infarction (MI). Here, we investigated the effect of fimasartan, a new ARB, on cardiac remodeling after MI. Sprague⁻Dawley rats were assigned into 3 groups: surgery only (sham group, n = 7), MI without (MI-only group, n = 13), and MI with fimasartan treatment (MI + Fima group, n = 16). MI was induced by the permanent ligation of the left anterior descending artery. Treatment with fimasartan (10 mg/kg) was initiated 24 h after MI and continued for 7 weeks. Rats in the MI + Fima group had a higher mean ejection fraction (66.3 ± 12.5% vs. 51.3 ± 14.8%, P = 0.002) and lower left ventricular end-diastolic diameter (9.14 ± 1.11 mm vs. 9.91 ± 1.43 mm, P = 0.045) than those in the MI-only group at 7 weeks after MI. The infarct size was lower in the MI + Fima than in the MI group (P < 0.05). A microarray analysis revealed that the expression of genes related to the lipid metabolism and mitochondrial membrane ion transporters were upregulated, and those involved in fibrosis and inflammation were downregulated by fimasartan. Fimasartan attenuates cardiac remodeling and dysfunction in rats after MI and may prevent the progression to heart failure after MI.

Keywords

angiotensin receptor blockercardiac remodelingfimasartanmicroarraymyocardial infarction

Figures

Figure 1
Figure 1 A schematic diagram of the experimental protocol. echo, echocardiography; Fima, fimasartan; MI, myocardial infarction; PCR, polymerase chain reaction; SD, Sprague–Dawley; PV, pressure–volume; w, week.
Figure 2
Figure 2 The anatomy and hemodynamics: (A) The chamber size measurement in M-mode, (B) the chamber size and ejection fraction of the rats during the experiment, and (C) the pressure–volume loops 7 weeks after MI. ■, sham; ▲, MI; ▼, MI + Fima. The MI + Fima group showed a smaller left ventricular volume and larger end-systolic pressure–volume relation (end-systolic pressure–volume relation, red line) compared with the MI-only group. EDPVR, end-diastolic pressure–volume relation; EDP, endo-diastolic pressure; ESPVR, end-systolic pressure–volume relationship; Fima, fimasartan; MI, myocardial infarction; LVEDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction. The P-values represent * P < 0.05, ** P < 0.01, and *** P < 0.001. The results are expressed as mean ± SEM (Standard Error Mean).
Figure 3
Figure 3 A histologic examination of the explanted hearts: (A) Cardiac hypertrophy was assessed as the heart weight/tibia length ratio. Fimasartan attenuated the induction of cardiac hypertrophy after MI. ■, sham; ▲, MI; ▼, MI + Fima. (B) The hematoxylin and eosin (H&E) and Masson trichrome (MT) staining showed a smaller infarct size and fibrosis in the MI + Fima group. (C) The MI + Fima group (■) had a smaller infarct size than the MI-only group (•). The P-values represent * P < 0.05, and ** P < 0.01. The results are expressed as mean ± SEM.
Figure 4
Figure 4 The transcriptional changes in the molecular pathways: (A) The microarray analysis in MI-only and MI + Fima group. In the MI + Fima group, 39 genes were upregulated and 19 genes were downregulated. (B) The clustering analysis showed the upregulation of lipid metabolism and mitochondria membrane ion transporter gene sets in the MI + Fima group. (C) The inflammation and fibrosis inducing genes were downregulated in the MI + Fima group.
Figure 5
Figure 5 The change in the cardiomyocyte remodeling and survival signaling with fimasartan: (A) TGF-beta was significantly decreased in the MI + Fima group. (B) The cardiac remodeling regulating molecule ERM and RhoA kinase activity were downregulated in the MI + Fima group. (C) The cell survival regulating molecule -catenin, PTEN, and PDK1 activity were upregulated in the MI + Fima group. The P-values represent * P < 0.05, ** P < 0.01, and *** P < 0.001. The results are expressed as mean ± SEM. ERM, Ezrin, Radoxin and Meosin; PTEN, phosphatase and tensin homologue; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; PDK1, Pyruvate Dehydrogenase Kinase 1.

그림 출처: PubMed Central 공개 논문 (PMC6463200)

Conflict of interest statement

The authors declare no conflict of interest.

그 밖의 정보
출판 형태
Journal Article
저널
Journal of clinical medicine · ISSN 2077-0383
전자 출판
2019-03-15
참고문헌
29편