In smooth muscle cell, there are key mediators of the proliferative effect… so the vessel has several walls that can proliferate without any control.

WHAT? PROLIFERATE LIKE A CANCER? YES

Several substances  stimulate smooth muscle cell growth and induces oxidative stress.

Oxidative stress is a specific cellular crisis, that can disturb normal cell rules. Oxidative stress is started by ROS (reactive oxigen species). When intracellular ROS production in  endothelial cells increases, smooth muscle starts to proliferate.    

Other factors are related with this proliferation: MMP (matrix  metalloproteinases). MMP are capable of degrading all kinds of extracellular matrix proteins associated with smooth muscle matrix cell proliferation and migration. MMP is expressed abundantly in atherosclerotic lesions and plays an important role in increasing VSMC (vessel smooth muscle cells). MMP react with inter cell matrix allowing individual cell migration.

SO… ROS allow proliferation while MMP allow migration…. we can say that «CAOS» BEGAN… Lúmen vessel get smaller and blood find a big obstacle to his passage.

In summary,  the proliferative effects of ET-1  (endothelial cells) involves an increase in the production of ROS. Further study of the signaling pathways involved may identify additional points at which ET-1-induced proliferation can be inhibited. Because antioxidants  and other these agents may be of benefit in preventing the SMC proliferation associated with pulmonary vascular diseases.