ACE inhibition promotes upregulation of endothelial progenitor cells and neoangiogenesis in cardiac pressure overload.
ABSTRACT Inhibition of the angiotensin-converting enzyme (ACE) prevents maladaptive cardiac remodelling. Endothelial progenitor cells (EPC) from the bone marrow contribute to endothelial repair and neovascularization, effects that are potentially important during cardiac remodelling. We hypothesized that ACE inhibitors may exert beneficial effects during pressure-induced myocardial hypertrophy by regulating progenitor cell function.
In C57/Bl6 mice, development of cardiac hypertrophy induced by transaortic constriction (TAC) for 5 weeks was reduced by ramipril, 5 mg/kg p.o., independent of blood pressure lowering. Ramipril prevented TAC-induced apoptosis of cardiac myocytes and endothelial cells. On day 1 after TAC, upregulation of Sca-1(pos)/KDR(pos) EPC was observed, which was further increased by ramipril. EPC were persistently elevated in the TAC mice receiving vehicle treatment but not in the ramipril group after 5 weeks. These effects were independent of hypoxia-inducible factor-1alpha mRNA and protein expression. The ACE inhibitor but not TAC improved the migratory capacity of DiLDL(pos) EPC. Increased cardiac afterload induced upregulation of extracardiac neoangiogenesis. This effect was enhanced by ACE inhibition. Ramipril but not TAC markedly increased cardiac capillary density determined by the ratio of CD31(pos) cells to cardiomyocytes. Bone marrow transplantation studies revealed that TAC increased the percentage of bone marrow-derived GFP(pos) endothelial cells in the myocardium, and ramipril made this effect more pronounced.
ACE inhibition prevents pressure-induced maladaptive cardiac hypertrophy and increases intra- and extracardiac neoangiogenesis associated with the upregulation of EPC and amelioration of EPC migration. The regulation of progenitor cells from the bone marrow identifies a novel effect of ACE inhibitors during cardiac remodelling.
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- "cytokines), could secrete kinins, acting on PC within the BM and facilitate their liberation. Protection of this chemotactic effect by the inhibition of ACE-mediated kinin degradation might contribute to the increased numbers of circulating PC seen under ACE inhibition, but not under Angiotensin (Ang) II receptor blockade (Wang, et al., 2006b; Benndorf et al., 2007; You et al., 2008; Müller et al., 2009). "
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ABSTRACT: The lack of myocardial repair after myocardial infarction and the heart failure that eventually ensues was thought of as proof that myocardial cell regeneration and myocardial repair mechanisms do not exist. Recently, growing experimental and clinical evidence has proven this concept wrong. Cardiac stem cells and endogenous myocardial repair mechanisms do exist; however, they do not produce significant myocardial repair. Similarly, the preliminary results of stem cell therapy for myocardial repair have shown early promise but modest results. Preclinical studies are the key to understanding stem cell senescence and lack of cellular contact and vasculature in the infarcted region. Additional laboratory studies are sure to unlock the therapeutic mechanisms that will be required for significant myocardial repair.Cardiology in review 11/2012; 21(3):111-20. DOI:10.1097/CRD.0b013e318289d7a9 · 3.24 Impact Factor
Conference Paper: Electric field measurement at sea[Show abstract] [Hide abstract]
ABSTRACT: Most of the electrometers are based on the measurement of the difference of potential between two electrodes; a major drawback of this method is its low performance since little of the signal energy is used. Indeed, a very small current goes through the equipment, limited by the high impedance of the voltmeter. The principle described by the author applies to the conducting media where an electric field creates a current density, as shown by the microscopic Ohm's law; this quantity is measured through an electrode of section S, using all the available energy for the detection: the signal-to-noise ratio is thus rising compared with the preceding approach. In this process, the main difficulty is to guarantee an input impedance equal to the resistance of the water volume substituted by the sensor, i.e. to avoid the current lines disturbance in the medium: this rule is general and applies to any probe of which the presence must not modify the measured value. The main characteristics of the corresponding sensor are presented in this paper; then, the behaviour of a three axis antenna is shown in real conditions-i.e. at seaOCEANS '97. MTS/IEEE Conference Proceedings; 11/1997