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Effects of combination of angiotensin-converting enzyme inhibitor and angiotensin receptor antagonist on inflammatory cellular infiltration and myocardial interstitial fibrosis after acute myocardial infarction

Cheuk-Man Yu, MD, FRACP^*, George L. Tipoe, MD, PhD, Kevin Wing-Hon Lai, Mphil^* and Chu-Pak Lau, MD, FACC^*

^* Division of Cardiology, Department of Medicine, Queen Mary Hospital, Hong Kong, China
Department of Anatomy, University of Hong Kong, Hong Kong, China

View larger version (117K): [in a new window]   Figure 1 Immunolocalization of activated cardiac myofibroblasts (A to E) and macrophages (F to J) in the infarct region two weeks after acute myocardial infarction (AMI). The activated myofibroblasts and macrophages were stained dark brown by anti-alpha-smooth muscle actin and anti-ED-1 antibodies, respectively. There was significant infiltration of activated myofibroblasts (B) and macrophages (G) after AMI that were not seen in the sham-operated rats (A and F). Treatment with fosinopril (C) decreased the infiltration of activated myofibroblasts, but not the macrophages (H). On the other hand, valsartan (D and I) and combined therapy of fosinopril and valsartan (E and J) significantly reduced the number of activated myofibroblasts and macrophages in the infarct zone (magnification 400x).

View larger version (83K): [in a new window]   Figure 2 Transforming growth factor-beta 1 (TGF-beta 1) messenger ribonucleic acid (mRNA) expression in different regions of the heart two weeks after acute myocardial infarction (AMI). Reverse transcription polymerase chain reaction was performed for RNA extracted from noninfarcted septum of the left ventricle and the right ventricle after AMI. In the noninfarcted septum, there was about twofold increase in TGF-beta 1 mRNA after AMI. Treatment with fosinopril (Fos) significantly decreased the amount of TGF-beta 1 mRNA expression in this region, while valsartan or a combination of fosinopril and valsartan (Fos + Val) normalized its expression. In the right ventricle, there was no significant change in TGF-beta 1 mRNA in any group. M = X174/HaeIII marker; Sham = sham-operated rats.