Left ventricular remodeling is a major cause of progressive heart failure and death after myocardial infarction. Although neoangiogenesis within the infarcted tissue is an integral component of the remodeling process, the capillary network is unable to support the greater demands of the hypertrophied myocardium, resulting in progressive loss of viable tissue, infarct extension and fibrous replacement. Here we show that bone marrow from adult humans contains endothelial precursors with phenotypic and functional characteristics of embryonic hemangioblasts, and that these can be used to directly induce new blood vessel formation in the infarct-bed (vasculogenesis) and proliferation of preexisting vasculature (angiogenesis) after experimental myocardial infarction. The neoangiogenesis resulted in decreased apoptosis of hypertrophied myocytes in the peri-infarct region, long-term salvage and survival of viable myocardium, reduction in collagen deposition and sustained improvement in cardiac function. The use of cytokine-mobilized autologous human bone-marrow-derived angioblasts for revascularization of infarcted myocardium (alone or in conjunction with currently used therapies) has the potential to significantly reduce morbidity and mortality associated with left ventricular remodeling.

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Implantation of the EDWARDS INTUITY Valve System is feasible, safe, and efficacious for aortic valve replacement. Aortic crossclamp and cardiopulmonary bypass times were reduced compared with those for conventional aortic valve replacement. Early hemodynamic performance was excellent and remained so up to 1 year.

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Cardiomyopathy (CM) comprises a heterogeneous group of diseases, including ischemic (ICM) and dilative (DCM) forms. The pathogenesis of primary DCM is not clearly understood. Recent studies in mice show that vascular endothelial growth factor (VEGF) is involved in ICM. Whether VEGF plays a role in human CM is unknown. We examined the mRNA and protein expression of VEGF and its receptors in hearts of patients with end-stage DCM and ICM and in healthy individuals using real-time polymerase chain reaction and Western blotting. Number of capillaries, area of myocytes, and collagen were calculated in cardiac biopsies using transmission electron microscopy. In DCM, except for VEGF-C, mRNA transcript levels of VEGF-A(165), VEGF-A(189), and VEGF-B and the protein level of VEGF-A and VEGF-R(1) were downregulated compared with controls (P:<0.05). However, in ICM, mRNA transcript levels of VEGF isoforms and protein levels of VEGF-C were upregulated. The vascular density was decreased in DCM but increased in ICM compared with controls (P:<0. 05). Muscular hypertrophy was not different for ICM and DCM, although DCM had more collagen (P:<0.05). Blunted VEGF-A and VEGF-R(1) protein expression and downregulated mRNA of the predominant isoform of VEGF-A, VEGF-A(165), to our knowledge shown here for the first time, provide evidence that the VEGF-A defect in DCM is located upstream. Whether downregulation of certain VEGF isoforms in DCM is a cause or consequence of this disorder remains unclear, although upregulated VEGF levels in ICM are most likely the result of ischemia.

, and S. Itescu. Myocardial neovascularization by bone marrow angioblasts results in cardiomyocyte regeneration. Am J Physiol Heart Circ Physiol 287: H525-H532, 2004; 10.1152/ ajpheart.00058.2004.-The primary cardiac response to ischemic insult is cardiomyocyte hypertrophy, which initiates a genetic program culminating in apoptotic myocyte loss, progressive collagen replacement, and heart failure, a process termed cardiac remodeling. Although a few cardiomyocytes at the peri-infarct region can proliferate and regenerate after injury, no approaches are known to effectively induce endogenous cardiomyocytes to enter the cell cycle. We recently isolated, in human adult bone marrow, endothelial progenitor cells, or angioblasts, that migrate to ischemic myocardium, where they induce neovascularization and prevent myocardial remodeling. Here we show that increasing the number of angioblasts trafficking to the infarct zone results in dose-dependent neovascularization with development of progressively larger-sized capillaries. This results in sustained improvement in cardiac function by mechanisms involving protection against apoptosis and, strikingly, induction of proliferation/ regeneration of endogenous cardiomyocytes. Our results suggest that agents that increase myocardial homing of bone marrow angioblasts could effectively induce endogenous cardiomyocytes to enter the cell cycle and improve functional cardiac recovery. stem cells; myocardial remodeling; myocardial infarction AN INTEGRAL COMPONENT of the healing process after a myocardial infarction is compensatory hypertrophy of viable cardiomyocytes at the peri-infarct rim to increase pump function in response to the loss of infarcted tissue (9, 24). However, cardiomyocyte hypertrophy initiates a genetic program that culminates in apoptotic loss of the cardiomyocytes, expansion of the initial infarct area, progressive collagen replacement, and heart failure (1,5,19,20), a process termed cardiac remodeling. Pharmacological means to prevent cardiomyocyte hypertrophy remain the mainstay of postinfarct therapy to prevent remodeling and heart failure. Recent observations have suggested that a second compensatory response of viable cardiomyocytes at the peri-infarct region is to proliferate and regenerate after injury (3, 7). Although cardiomyocyte regeneration can be accomplished by providing exogenous precursors, for example, from the bone marrow (17), no approaches are known to effectively induce endogenous cardiomyocytes to enter the cell cycle.We recently put forward the hypothesis that hypertrophied cardiomyocytes undergo apoptosis, because the endogenous capillary network cannot provide the compensatory increase in perfusion required for cell survival (12). Vascular network formation is the result of a complex process that begins in the prenatal period with induction of vasculogenesis by hemangioblasts, cells derived from the human ventral aorta that give rise to endothelial and hematopoietic elements (4, 6, 10, 13). Postnatal vasculogenesis occurs via pathways ...

Prophylactic administration of CMVIG after solid organ transplantation is associated with improved total survival, reduced CMV disease, and CMV-associated deaths.