AIM: The regulation of angiogenesis in the hypertrophied overloaded heart is incompletely understood. Bone-marrow-derived progenitor cells have been shown to contribute to endothelial homeostasis, repair, and new blood vessel formation. We therefore studied the effects of pressure overload on angiogenesis and progenitor cells. METHODS AND RESULTS: Pressure overload induced by transaortic constriction (TAC, C57/Bl6 mice, 360 microm for 35 days) increased left ventricular (LV) systolic pressure, the ratio of heart weight to tibia length, cardiomyocyte diameters, and cardiac apoptosis and fibrosis compared to sham-operated mice. In the TAC group, the number of cycling Ki67 pos cells increased from none to 0.1 +/- 0.02% in cardiomyocytes and from 0.17 +/- 0.02% to 0.65 +/- 0.1% in non-cardiomyocytes, P < 0.001. stem cell antigen 1(pos)/vascular endothelial growth factor receptor 2 pos endothelial progenitor cells (EPC) increased to 210 +/- 25% in the blood and to 196 +/- 21% in the bone marrow (P < 0.01). TAC upregulated cultured spleen-derived DiLDL pos/lectin pos EPC to 221 +/- 37%, P < 0.001. Cardiac hypertrophy and upregulation of EPC secondary to cardiac pressure overload were associated with increased extra-cardiac neoangiogenesis (54 +/- 12% increase, P < 0.05). In endothelial nitric oxide synthase double knockout mice, the upregulation of EPC by TAC was abolished. Maladaptive myocardial remodelling in TAC mice was characterized by a reduction of CD31 pos cells. In mice transplanted with green fluorescent protein pos bone marrow, TAC markedly increased myocardial bone marrow-derived CD31 pos cells from 2.37 +/- 0.4% to 7.76 +/- 1.5% and MEF2 pos cells from 1.8 +/- 0.4/mm2 to 20.5 +/- 5.3/mm2, P < 0.05. CONCLUSION: Pressure-induced myocardial hypertrophy leads to upregulation of systemic EPCs, increased extra-cardiac angiogenesis, and upregulation of intra-myocardial bone marrow-derived endothelial and myocyte precursor cells. The data show that afterload-dependent regulation of bone marrow-derived progenitor cells contributes to angiogenesis in myocardial hypertrophy.
AIM: The regulation of angiogenesis in the hypertrophied overloaded heart is incompletely understood. Bone-marrow-derived progenitor cells have been shown to contribute to endothelial homeostasis, repair, and new blood vessel formation. We therefore studied the effects of pressure overload on angiogenesis and progenitor cells. METHODS AND RESULTS: Pressure overload induced by transaortic constriction (TAC, C57/Bl6 mice, 360 microm for 35 days) increased left ventricular (LV) systolic pressure, the ratio of heart weight to tibia length, cardiomyocyte diameters, and cardiac apoptosis and fibrosis compared to sham-operated mice. In the TAC group, the number of cycling Ki67 pos cells increased from none to 0.1 +/- 0.02% in cardiomyocytes and from 0.17 +/- 0.02% to 0.65 +/- 0.1% in non-cardiomyocytes, P < 0.001. stem cell antigen 1(pos)/vascular endothelial growth factor receptor 2 pos endothelial progenitor cells (EPC) increased to 210 +/- 25% in the blood and to 196 +/- 21% in the bone marrow (P < 0.01). TAC upregulated cultured spleen-derived DiLDL pos/lectin pos EPC to 221 +/- 37%, P < 0.001. Cardiac hypertrophy and upregulation of EPC secondary to cardiac pressure overload were associated with increased extra-cardiac neoangiogenesis (54 +/- 12% increase, P < 0.05). In endothelial nitric oxide synthase double knockout mice, the upregulation of EPC by TAC was abolished. Maladaptive myocardial remodelling in TAC mice was characterized by a reduction of CD31 pos cells. In mice transplanted with green fluorescent protein pos bone marrow, TAC markedly increased myocardial bone marrow-derived CD31 pos cells from 2.37 +/- 0.4% to 7.76 +/- 1.5% and MEF2 pos cells from 1.8 +/- 0.4/mm2 to 20.5 +/- 5.3/mm2, P < 0.05. CONCLUSION: Pressure-induced myocardial hypertrophy leads to upregulation of systemic EPCs, increased extra-cardiac angiogenesis, and upregulation of intra-myocardial bone marrow-derived endothelial and myocyte precursor cells. The data show that afterload-dependent regulation of bone marrow-derived progenitor cells contributes to angiogenesis in myocardial hypertrophy.
Authors: Monte S Willis; Laura A Dyer; Rongqin Ren; Pamela Lockyer; Isabel Moreno-Miralles; Jonathan C Schisler; Cam Patterson Journal: Cardiovasc Pathol Date: 2012-11-28 Impact factor: 2.185
Authors: Karen C Young; Eneida Torres; Konstantinos E Hatzistergos; Dorothy Hehre; Cleide Suguihara; Joshua M Hare Journal: Circ Res Date: 2009-05-07 Impact factor: 17.367
Authors: Seung Kyum Kim; Lauren A Biwer; M Elizabeth Moss; Joshua J Man; Mark J Aronovitz; Gregory L Martin; Francisco J Carrillo-Salinas; Ane M Salvador; Pilar Alcaide; Iris Z Jaffe Journal: Circ Heart Fail Date: 2021-02-01 Impact factor: 8.790
Authors: Maria E Marketou; Fragiskos I Parthenakis; Athanasia Kalyva; Charalampos Pontikoglou; Spyros Maragkoudakis; Joanna E Kontaraki; Evangelos A Zacharis; Gregory Chlouverakis; Alexandros Patrianakos; Helen A Papadaki; Panos E Vardas Journal: J Clin Hypertens (Greenwich) Date: 2014-10-20 Impact factor: 3.738
Authors: Maria E Marketou; Athanasia Kalyva; Fragiskos I Parthenakis; Charalampos Pontikoglou; Spyros Maragkoudakis; Joanna E Kontaraki; Gregory Chlouverakis; Evangelos A Zacharis; Alexandros Patrianakos; Helen A Papadaki; Panos E Vardas Journal: J Clin Hypertens (Greenwich) Date: 2014-03-19 Impact factor: 3.738