Selective downregulation of VEGF-A(165), VEGF-R-1, and decreased capillarydensity in patients with dilative but not ischemic cardiomyopathy

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 endothel ial growth factor (VEGF) is involved in ICM. Whether VEGF plays a role in h uman Chi is unknown. We examined the mRNA and protein expression of VEGF an d its receptors in hearts of patients with end-stage DCM and ICM and in hea lthy individuals using real-time polymerase chain reaction and Western blot ting. 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 w ith controls (P<0.05). However, in ICM, mRNA transcript levels of VEGF isof orms and protein levels of VEGF-C were upregulated, The vascular density wa s decreased in DCM but increased in ICM compared with controls (P<0.05). Mu scular 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 down regulated mRNA of the predominant isoform of VEGF-A, VEGF-A(165), to our kn owledge shown hero for the first time, provide evidence that the VEGF-A def ect in DCM is located upstream. Whether downregulation of certain VEGF isof orms in DCM is a cause or consequence of this disorder remains unclear, alt hough upregulated VEGF levels in ICM are most likely the result of ischemia .