Question: 

The lung is the only organ that receives the whole stroke volume oft he heart. Any dysfunction oft he left ventricle forms a reverse stress to the pulmonary vessels with an increased risk of pulmonary oedema and pressure overload to the right ventricle. In contrast, selective failure oft he right ventricle leads to a reduced perfusion oft he pulmonary vessels and may be initiated by a pressure overload of the right ventricle. We analyzed pulmonary remodelling in response to cardiac events such as selective left and right heart failure. We focused on the PTHrP system that triggers typ-II alveolar cell communication with lipofibroblasts. An activation of PTHrP rezeptors increases the formation of PPARg, leptin, und adipocyte differentiation-related protein (ADRP). Leptin causes a positive feedback-mechanism for pulmonary PTHrP-formation. Leptin knockout mice have reduced expression of PTHrP. Lack of PTHrP/PTHrP rezeptor interaction leads to a transdifferentiation of lipofibroblasts to myofibroblasts and increases pulmonary stiffness.

Methodology: 

Left ventricular heart failure was induced by crossing transgenic TGF-b overexpressing mice with eNOS-/- mice resulting in TG-eNOS+/- mice. Right heart failure was induced by exposing mice to hypoxia for 4 weeks.

Results: 

As a result of left heart failure lung wet weight to body weight ratio was increased (4.95±0.34 vs. 6.80±0.18 mg/g). In these lungs PTHrP receptor mRNA expression was increased (+1.88-fold) as well as ADRP (+1.93-fold) and PPAR-g (+1.62-fold). Hypoxie also led to a comparbale increase of lung wet weight (8.72±0.41 vs. 5.86±0.14 mg/g), increased PTHrP receptor expression (+1.48-fold), but not to a subsequent increase of ADRP (+1.22-fold) or PPARg (+1.36-fold). The latter one had an increased collagen expression (2.24-fold).

Conclusion: 

The data show for the first time thart cardiac-dependent events directly induce a PTHrP receptor linked remodelling process. As PTHrP is responsible for dilatation of pulmonary vessels, compliance of the lung and formation of surfactants the observed differences between right and left ventricular events on pulmonary PTHrP receptor expression indicate a lung-specific adaptation to both disease states.