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Additive effects of endothelial progenitor cells combined with ACE inhibition and β-blockade on left ventricular function following acute myocardial infarction

University of Melbourne, Department of Medicine, St Vincent's Hospital, Princes St, Fitzroy 3065, Victoria, Australia, aboyle@medstv. unimelb.edu.au, Columbia University, College of Physicians and Surgeons, 14-402 630 West, 168th St New York, NY

Michael Schuster

Columbia University, College of Physicians and Surgeons, 14-402 630 West, 168th St New York, NY

Piotr Witkowski

Columbia University, College of Physicians and Surgeons, 14-402 630 West, 168th St New York, NY, Medical University of Gdansk, Gdansk, Poland

Guosheng Xiang

Columbia University, College of Physicians and Surgeons, 14-402 630 West, 168th St New York, NY

Tetsunori Seki

Columbia University, College of Physicians and Surgeons, 14-402 630 West, 168th St New York, NY

Kerrie Way

University of Melbourne, Department of Medicine, St Vincent's Hospital, Princes St, Fitzroy 3065, Victoria, Australia, Columbia University, College of Physicians and Surgeons, 14-402 630 West, 168th St New York, NY

Silviu Itescu

University of Melbourne, Department of Medicine, St Vincent's Hospital, Princes St, Fitzroy 3065, Victoria, Australia, Columbia University, College of Physicians and Surgeons, 14-402 630 West, 168th St New York, NY

Animal studies have demonstrated the efficacy of endothelial progenitor cells (EPCs) in preventing left ventricular (LV) remodelling following myocardial infarction (MI). Preliminary human studies are underway, yet no studies have demonstrated efficacy in combination with standard medical therapy, i.e. angiotensin-converting enzyme (ACE) inhibitors and β-blockers. Nude rats underwent left anterior descending coronary artery ligation to induce MI. Animals were randomised to receive no treatment (MI, n=5), quinapril 200 mg/L + metoprolol 2 g/L (ACE/BB, n=5), two million EPCs intravenously (EPC, n=5)or both (ACE/BB + EPC [n=5]), then sacrificed after two weeks treatment. ACE/BB resulted in a 75% reduction in fibrosis in the region remote from the MI (p<0.05), but EPC therapy had little effect here. Conversely, EPC therapy induced neovascularisation at the peri-infarct rim, thereby preventing peri-infarct apoptosis by 81% (p<0.05). Acting via different but complementary mechanisms, the combination of ACE/BB + EPCs resulted in a greater overall improvement in LV function on echocardiography than either therapy alone. Clinical trials using stem cell therapy in conjunction with standard medical treatment are warranted.

Key Words: stem cell • myocardial infarction • remodelling • heart failure

Journal of Renin-Angiotensin-Aldosterone System, Vol. 6, No. 1, 33-37 (2005)
DOI: 10.3317/jraas.2005.004


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