Abstract
Pulmonary arterial hypertension (PAH) is a fatal disease characterized by a progressive increase in pulmonary vascular resistance and vascular remodeling leading to right heart failure and early death. The pathology of PAH is associated with endothelium dysfunction and vascular remodeling in pulmonary arteries. In diseased pulmonary arteries, the balance between matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) is broken down. In this process, TIMP are up-regulated, which inhibits MMP, promotes extracellular matrix (ECM) deposition and finally leads to vascular remodeling. So, what would happen to PAH if the expression of TIMP was down-regulated in diseased pulmonary vessels? We hypothesize that the attenuation of TIMP at the advanced stage of PAH might reverse severe PAH, via ameliorating vascular remodeling and endothelium repair.
Acknowledgments
This research project has been partially supported by the National Natural Science Foundation of China (NSFC 30801500 and 81070040), Program for New Century Excellent Talents in University (NCET-08-0488), Zhejiang Provincial Natural Science Foundation of China (ZJNSF Y2080369).
Disclosure: we have no financial or personal relationships with other people or organizations to report that caused a conflict of interest in writing this paper.