Endothelial cells and pulmonary arterial hypertension: apoptosis, proliferation, interaction and transdifferentiation

Severe pulmonary arterial hypertension, whether idiopathic or secondary, is characterized by structural alterations of microscopically small pulmonary arterioles. The vascular lesions in this group of pulmonary hypertensive diseases show actively proliferating endothelial cells without evidence of apoptosis. In this article, we review pathogenetic concepts of severe pulmonary arterial hypertension and explain the term "complex vascular lesion ", commonly named "plexiform lesion", with endothelial cell dysfunction, i.e., apoptosis, proliferation, interaction with smooth muscle cells and transdifferentiation

The role of the mitochondrion in smooth muscle cell fate choices of proliferation versus apoptosis during vascular and cardiovascular diseases

The role of the mitochondrion in cellular metabolism has, in recent years, become more pronounced beyond its traditional role of the energy supplier in the cell. Now the mitochondrion is known to have the duties of biosynthesis, and is involved in programmed cell death (apoptosis). There are pathophysiological incidences where the cell is stressed and must make a choice between survival (including proliferating) and apoptosis. It is unknown how the cell chooses between these two fates, but the mitochondrion may play a role in at least the series of steps leading to apoptosis or proliferation. In this paper it is proposed that the mitochondria may be a lynchpin through which this decision is made. It is suggested that the production of reactive oxygen species (ROS) originating from the mitochondrion may produce the signalling molecules which drive the cell down either a proliferative pathway or one of programmed cell death. These peroxidised molecules may alter the phosphatase/kinase activities in the cell, determine the cell fate and play a central role in the pathogenesis of several vascular pathologies. If so, the mitochondrion may be the key in producing the signalling molecules necessary for dictating cell fate choice