© 2000 American Heart Association, Inc.
Clinical Research |
Selective Downregulation of VEGF-A165, VEGF-R1, and Decreased Capillary Density in Patients With Dilative but Not Ischemic Cardiomyopathy
From the Laboratory for Cardiovascular Research, Departments of Anatomy (D.A., R.B., P.P., H.T. S.A.), Molecular Biology (R.H., R.S.), and Cardio-Thoracic Surgery (A.K.), University of Vienna and Department of Medicine, St. Elisabeth Hospital (A.M.), Vienna, Austria
Correspondence to S. Aharinejad, MD, Laboratory for Cardiovascular Research, First Department of Anatomy, University of Vienna, Waehringerstrasse 13, A-1090 Vienna, Austria. E-mail ahas{at}univie.ac.at
Abstract—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-A165, VEGF-A189, and VEGF-B and the protein level of VEGF-A and VEGF-R1 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-R1 protein expression and downregulated mRNA of the predominant isoform of VEGF-A, VEGF-A165, 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.
Key Words: cardiomyopathy • growth factors • angiogenesis
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