This authoritative review from eminent translational researchers in this field demonstrates the diversity of K+ channels which regulates the pulmonary arterial and venous circulations. It raises the question as to why there has not been the development of K+ channel activator drugs as a treatment, as there appears to be an extraordinary opportunity and need for such therapies.
Interesting research demonstrating that the loss of BMPR2 signaling, an established fundamental mechanism underlying PAH, is mediated by downregulation of K+ channels of the voltage regulated family. This implies that K+ downregulation may be a cause of pulmonary vasoconstriction and that K+ channel activators may be a promising treatment.
This authoritative review from a leading authority in the field explains the complex pathophysiology behind the development of pulmonary hypertension which may apply to all of the 5 groups of clinical pulmonary hypertension.
This is a report of preclinical research that studied the role of K+(V.7) channels in PAH. Unlike other K+ channels that appear to be downregulated in PAH, the Kv7 channel function was preserved whereas the KCNE4 subunit was upregulated. This research highlights the complexities behind K+ channel control over the pulmonary circulation and the impact of their actions.
Detailed review of the role of PDGF in PAH. The authors provide solid evidence that inhibition of PDGFR signaling by imatinib mesylate represents an encouraging therapeutic concept and is likely to become an additional targeted therapy for PAH. In addition to existing therapies, this anti-proliferative approach has the potential to establish a sustained reduction of the underlying pulmonary vascular remodeling.
The downregulation of K+ channels has been considered a hallmark of pulmonary hypertension. This paper specifically reviews their role in PAH. The lack of any candidate drugs is largely the reason that this seems to be unrecognized in the clinical arena. K+ channels appear to regulate pulmonary vascular tome and proliferation.