Can angiogenesis be exercised?
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Animals↗
Biomedical subjects
Jalees Rehman
Publications and source records attributed to Jalees Rehman.
Exercise acutely increases circulating endothelial progenitor cells and monocyte-/macrophage-derived angiogenic cells.
OBJECTIVES: We investigated whether a single episode of exercise could acutely increase the numbers of endothelial progenitor cells (EPCs) and cultured/circulating angiogenic cells (CACs) in human subjects. BACKGROUND: Endothelial progenitor cells and CACs can be isolated from peripheral blood and have been shown to participate in vascular repair and angiogenesis. We hypothesized that exercise may acutely increase either circulating EPCs or CACs. METHODS: Volunteer subjects (n = 22) underwent exhaustive dynamic exercise. Blood was drawn before and after exercise, and circulating EPC numbers as well as plasma levels of angiogenic growth factors were assessed. The CACs were obtained by culturing mononuclear cells and the secretion of multiple angiogenic growth factors by CACs was determined. RESULTS: Circulating EPCs (AC133+/VE-Cadherin+ cells) increased nearly four-fold in peripheral blood from 66 +/- 27 cells/ml to 236 +/- 34 cells/ml (p < 0.05). The number of isolated CACs increased 2.5-fold from 8,754 +/- 2,048 cells/ml of peripheral blood to 20,759 +/- 4,676 cells/ml (p < 0.005). Cultured angiogenic cells isolated before and after exercise showed similar secretion patterns of angiogenic growth factors. CONCLUSIONS: Our study demonstrates that exercise can acutely increase EPCs and CACs. Given the ability of these cell populations to promote angiogenesis and vascular regeneration, the exercise-induced cell mobilization may serve as a physiologic repair or compensation mechanism.
Adult↗
Reduced pericardial levels of endostatin correlate with collateral development in patients with ischemic heart disease.
OBJECTIVES: We investigated whether pericardial levels of a pro-angiogenic factor (vascular endothelial growth factor, VEGF) or an anti-angiogenic factor (endostatin) related to the presence of coronary collateral circulation in patients with significant coronary artery disease (CAD). BACKGROUND: Coronary collateralization favorably alters the prognosis of patients with occlusive CAD. The specific factors that mediate and maintain collateral formation in coronary vessel occlusion are yet to be identified. METHODS: Coronary angiograms from 39 patients undergoing coronary artery bypass surgery were evaluated for the absence of collaterals (n = 20) or the presence of Rentrop classification grade 3 collaterals (n = 19). Pericardial fluid samples were obtained at the time of surgery and were assayed for the VEGF and endostatin by enzyme-linked immunosorbent assay comparing the two groups of patients. RESULTS: Vascular endothelial growth factor levels were not significantly different between the groups (28.86 +/- 4.67 pg/ml vs. 24.39 +/- 3.08 pg/ml, p = 0.43). However, pericardial fluid endostatin levels were nearly 40% lower in patients with grade 3 collateralization compared with those lacking angiographic evidence of collaterals (15.17 +/- 1.87 ng/ml vs. 24.25 +/- 2.08 ng/ml, p < 0.0025). CONCLUSIONS: Pericardial fluid levels of endostatin, but not VEGF, are associated with the presence or absence of collaterals in patients with CAD. These data suggest that the angiogenesis inhibitor endostatin levels may locally modulate coronary collateral formation.
Aged↗
Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells.
BACKGROUND: The delivery of autologous cells to increase angiogenesis is emerging as a treatment option for patients with cardiovascular disease but may be limited by the accessibility of sufficient cell numbers. The beneficial effects of delivered cells appear to be related to their pluripotency and ability to secrete growth factors. We examined nonadipocyte stromal cells from human subcutaneous fat as a novel source of therapeutic cells. METHODS AND RESULTS: Adipose stromal cells (ASCs) were isolated from human subcutaneous adipose tissue and characterized by flow cytometry. ASCs secreted 1203+/-254 pg of vascular endothelial growth factor (VEGF) per 10(6) cells, 12 280+/-2944 pg of hepatocyte growth factor per 10(6) cells, and 1247+/-346 pg of transforming growth factor-beta per 10(6) cells. When ASCs were cultured in hypoxic conditions, VEGF secretion increased 5-fold to 5980+/-1066 pg/10(6) cells (P=0.0016). The secretion of VEGF could also be augmented 200-fold by transfection of ASCs with a plasmid encoding VEGF (P<0.05). Conditioned media obtained from hypoxic ASCs significantly increased endothelial cell growth (P<0.001) and reduced endothelial cell apoptosis (P<0.05). Nude mice with ischemic hindlimbs demonstrated marked perfusion improvement when treated with human ASCs (P<0.05). CONCLUSIONS: Our experiments delineate the angiogenic and antiapoptotic potential of easily accessible subcutaneous adipose stromal cells by demonstrating the secretion of multiple potentially synergistic proangiogenic growth factors. These findings suggest that autologous delivery of either native or transduced subcutaneous ASCs, which are regulated by hypoxia, may be a novel therapeutic option to enhance angiogenesis or achieve cardiovascular protection.
Adipose Tissue↗
Obesity is associated with increased levels of circulating hepatocyte growth factor.
OBJECTIVES: This study evaluated whether obesity in humans was associated with an increase in circulating hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) levels. BACKGROUND: Obesity acts as a cardiovascular risk factor by mechanisms that are not fully understood. Adipose tissue is able to secrete multiple cytokines and growth factors ex vivo. We hypothesized that the increased presence of adipose tissue in obese subjects results in systemic elevations of the mitogenic factors HGF and VEGF. METHODS: Blood samples were obtained from lean (n = 21) and obese (n = 44) volunteers. Serum HGF and VEGF levels were assessed by enzyme-linked immunoadsorbent assay. Insulin and fasting glucose levels were measured to evaluate insulin sensitivity. Conditioned medium of adipose cells was assayed for HGF secretion. RESULTS: Serum HGF levels in obese subjects were more than three-fold higher than those of lean subjects (2,462 +/- 184 pg/ml vs. 765 +/- 48 pg/ml, p < 0.0001). The VEGF levels were not significantly elevated in obese subjects (135 +/- 31 pg/ml vs. 128 +/- 37 pg/ml). The HGF concentrations, but not VEGF concentrations, were significantly correlated with body mass index (BMI) (p < 0.0001, r = 0.74). The observed increases in HGF concentrations of obese subjects were not secondary to insulin resistance or hypertension. Freshly isolated human adipose cells secreted HGF. CONCLUSIONS: Our results indicate that obesity is associated with a marked increase in circulating HGF levels, which correlate linearly with BMI. Because vascular growth factors have been associated with the pathogenesis of atherosclerosis, the possible role of such humoral factors as a link between obesity and cardiovascular disease is very intriguing.
Adipocytes↗
Peripheral blood "endothelial progenitor cells" are derived from monocyte/macrophages and secrete angiogenic growth factors.
BACKGROUND: Endothelial progenitor cells (EPCs) have been isolated from peripheral blood and can enhance angiogenesis after infusion into host animals. It is not known whether the proangiogenic effects are a result of such events as endothelial differentiation and subsequent proliferation of EPCs or secondary to secretion of angiogenic growth factors. METHODS AND RESULTS: Human EPCs were isolated as previously described, and their phenotypes were confirmed by uptake of acetylated LDL and binding of ulex-lectin. EPC proliferation and surface marker expression were analyzed by flow cytometry, and conditioned medium was assayed for growth factors. The majority of EPCs expressed monocyte/macrophage markers such as CD14 (95.7+/-0.3%), Mac-1 (57.6+/-13.5%), and CD11c (90.8+/-4.9%). A much lower percentage of cells expressed the specific endothelial marker VE-cadherin (5.2+/-0.7%) or stem/progenitor-cell markers AC133 (0.16+/-0.05%) and c-kit (1.3+/-0.7%). Compared with circulating monocytes, cultured EPCs showed upregulation of monocyte activation and macrophage differentiation markers. EPCs did not demonstrate any significant proliferation but did secrete the angiogenic growth factors vascular endothelial growth factor, hepatocyte growth factor, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor. CONCLUSIONS: Our findings suggest that acetylated LDL(+)ulex-lectin(+) cells, commonly referred to as EPCs, do not proliferate but release potent proangiogenic growth factors. The majority of acetylated LDL(+)ulex-lectin(+) cells are derived from monocyte/macrophages. The findings of low proliferation and endothelial differentiation suggest that their angiogenic effects are most likely mediated by growth factor secretion. These findings may allow for development of novel angiogenic therapies relying on secreted growth factors or on recruitment of endogenous monocytes/macrophages to sites of ischemia.
Angiogenesis Inducing Agents↗