Selective Downregulation of VEGF-A 165 , VEGF-R 1 , and Decreased Capillary Density in Patients With Dilative but Not Ischemic Cardiomyopathy

• Published in: Circulation research Vol. 87; no. 8; pp. 644 - 647
• Main Authors: Abraham, Dietmar, Hofbauer, Reinhold, Schäfer, Romana, Blumer, Roland, Paulus, Patrick, Miksovsky, Aurelia, Traxler, Hannes, Kocher, Alfred, Aharinejad, Seyedhossein
• Format: Journal Article
• Language: English
• Published: 13.10.2000
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.RES.87.8.644

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-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.