Additive effects of endothelial progenitor cells combined with ACE inhibition and beta-blockade on left ventricular function following acute myocardial infarction.
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 beta-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.
Boyle
Andrew J
AJ
University of Melbourne, Department of Medicine, St Vincent's Hospital, Fitzroy, Victoria, 3065, Australia. aboyle@medstv.unimelb.edu.au
Schuster
Michael
M
Witkowski
Piotr
P
Xiang
Guosheng
G
Seki
Tetsunori
T
Way
Kerrie
K
Itescu
Silviu
S
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D042783:Endothelial Cells / Q000637:transplantation*; D005109:Extracellular Matrix / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism; D018919:Neovascularization, Physiologic; D051381:Rats; D011919:Rats, Inbred Strains; D011923:Rats, Nude; D033581:Stem Cell Transplantation; D016277:Ventricular Function, Left / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors