Pneumologie 2011; 65 - P175
DOI: 10.1055/s-0031-1272118

Contribution of progenitor cells in experimental right heart hypertrophy induced by pulmonary artery ligation

H Luitel 1, A Sydykov 1, B Kojonazarov 1, BK Dahal 1, D Kosanovic 1, W Seeger 1, F Grimminger 1, HA Ghofrani 1, RT Schermuly 1
  • 1Lungs and Heart Research Gießen

Background:

Right ventricular hypertrophy (RVH) is an adaptive response to increased hemodynamic load. Previous studies on pulmonary hypertension and RV remodeling processes have reported different mechanisms in right ventricular remodeling, however, the contribution of progenitor cells and their homing mechanism is still unclear.

Methods:

RV hypertrophy was induced in male C57Bl/6 mice by pulmonary artery banding (PAB). The functional changes of RV were assessed by ultrasound biomicroscopy (UBM) and correlated with invasive measurements. Further we assessed RV fibrosis, cardiac myocyte size and expression of hypertrophic and stem cell marker genes at the mRNA level.

Results:

Right ventricular remodeling in banded mice was characterized by dilatation and increased free wall thickness of the RV, flattening of the interventricular septum and compression of the left ventricle. The RV wall thickness was not significantly different between PAB and sham-operated mice at postoperative day 1 but progressively increased in PAB mice by day 14 and showed no further significant increase. RV function evaluated by TAPSE and Tei index significantly deteriorated immediately after PAB. Furthermore, we validated the results of echocardiographic investigations by necropsy and found a good correlation of echocardiographic parameters with heart mass at necropsy. Histological examination revealed a significant and progressive increase in RV collagen deposition and cardiomyocyte hypertrophy in the PAB mice. The RV remodeling process in PAB mice was associated with a significant increase in the expression of hypertrophic, profibrotic and stem cell marker genes in mRNA level.

Conclusions:

Our finding of increased expression of stem cell marker genes suggests contribution of progenitor cells to RV remodeling process. Currently we are investigating the role of progenitor cells in RV remodeling using chimeric mice generated by BM transplantation from eGFP transgenic mice into lethaly irradiated animals.