Changes in Myocardial Microvascularisation After Heart Transplantation and During Cardiac Allograft Vasculopathy

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M.M.H. Huibers, F. van Pijpen, H.J.H. Kirkels, N. de Jonge, A. Vink, R.A. de Weger

Chair(s): Prof. dr. C.C. Baan & dr. M.R. Rookmaaker

Wednesday 8 march 2017

18:18 - 18:30h at Hendrik Marsmanzaal

Categories: Parallel - Basaal

Parallel session: Parallelsessie V – Basaal 1 - Analyse niet-hematopoietische cellen in orgaantransplantatie

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Cardiac allograft vasculopathy (CAV) is a major threat to long-term survival of heart transplantation (HTx) recipients. Impaired microvascular structure and function have been shown to be present in heart failure and contribute to disease progression. However, limited research has been conducted into myocardial microvasculature after HTx and development of CAV. The aim of this study is to investigate microvascular density in the myocardium of HTx recipients and relate this to angiogenic gene expression. We hypothesize microvascular density to be decreased and angiogenic pathways to be downregulated in CAV patients.

Transversal mid ventricular heart slices were obtained from HTx recipients at autopsy. The cohort consists of 16 CAV negative patients who died within 0.5 years following HTx and 18 CAV positive patients who were diagnosed with CAV via histological evaluation of the coronary arteries post-mortem. Immunohistochemical staining (CD31) was used to study microvascular density in three layers of the myocardium (inner,- mid-, and outer myocardium). qPCR targeting 10 established angiogenesis and/or CAV related genes was performed to study gene expression (angiogenesis inhibitors: PF4, ET-1, TSP-1 and angiogenesis stimulating: VEGF-A, VEGF-C, Hif-1α, CD105, Notch1, FGF1, NOS3).

Microvascular density was increased in the outer layer of the heart of CAV positive HTx recipients compared to CAV negative recipients. Interestingly, the CAV positive group show much more interindividual variance in microvascular density compared to the CAV negative group. For overall gene expression, a trend towards upregulation was seen both the CAV positive and the CAV negative group compared to the cardiac tissue without transplantation. A mixed profile of pro- and anti-angiogenic genes was found to be upregulated in CAV positive patients.

Microvascular density is increased in the outer layer of the heart of HTx recipients with CAV compared to HTx recipients without CAV. An increased expression of angiogenesis stimulating and inhibiting genes was found in CAV patients. Combined, these findings suggest the activation of compensatory mechanisms. Due to the differences in microvascular density in the different layers of the heart, endomyocardial biopsies might not give a representative estimation of microvascular density for other layers in the heart.