Hv1 proton channel possibly promotes atherosclerosis by regulating reactive oxygen species production.

Atherosclerosis and its fatal complications, such as myocardial infarction or stroke, represent the most common cause of morbidity or mortality in modern world. It was observed that an excess of reactive oxygen species (ROS) accompanies atherosclerosis. Under physiological circumstances, intracellular H(+) accumulates and cell membrane depolarizes during ROS production, rendering ROS generation self-limiting and thus avoiding oxidative stress. However, the persistent production of ROS during atherosclerosis suggests that the physiologically self-limiting ROS-generating process was somehow disrupted and there may be an as-yet unknown mechanism supporting unlimited ROS generation. We thus postulated that an outward H(+) conductance, which can efficiently export H(+) from the cytosol and maintain membrane potential, may play a crucial role during atherosclerosis. So far, Hv1 channels were mainly found in immune cells (macrophages, neutrophils). As large quantities of vascular infiltrating macrophages exist, we proposed that Hv1-mediated oxidative stress promoted excessive ROS production and the formation of foam cells, contributing to atherosclerosis. In addition, we could not exclude the possibility that Hv1 channels may be upregulated in vascular cells under atherosclerotic conditions, which may also exert effects on vascular inflammation and fibrous cap formation. The present study will employ Hv1 knockout mice in combination with in vitro studies to explore the role of Hv1 channel in atherosclerosis and dissect the underlying mechanisms. The results are expected to offer novel insights into the pathogenesis of atherosclerosis as well as clues for developing novel therapeutic avenues.