This Readership is 10 times more when compared to other Subscription Journals (Source: Google Analytics)
All submissions of the EM system will be redirected to Online Manuscript Submission System. Authors are requested to submit articles directly to Online Manuscript Submission System of respective journal.
ncreased proliferation and survival of pulmonary arterial vascular smooth muscle cells (PAVSMC) coupled with metabolic
shift to glycolysis are key pathophysiological components of vascular remodeling in PAH, molecular mechanisms of which are
not fully understood. Mammalian target of rapamycin (mTOR), a central controller of cell growth, proliferation and survival, acts
through two distinct complexes, rapamycin-sensitive mTORC1 that modulates cell growth and rapamycin-resistant mTORC2
that activates Akt. The importance of mTORC1 for VSMC proliferation and pulmonary vascular remodeling is demonstrated
by the use of rapamycin. The role of mTORC2 in PAVSMC metabolism, proliferation and survival in PAH is not known. We
demonstrate that mTORC2-Akt signaling is up-regulated in PAVSMC from subjects with idiopathic PAH (iPAH) and from
rats with chronic hypoxia-induced pulmonary hypertension (PH) in vivo and in vitro. We also found that human iPAH and
rat PH PAVSMC have elevated cellular energy levels, proliferation and survival that fully depend on glycolytic metabolism.
Importantly, inhibition of mTORC2 signaling by siRNA rictor or specific Akt1/2 inhibitor decreases cellular energy levels and
inhibits human iPAH and rat PH PAVSMC proliferation via activation of energy sensor AMPK. mTORC2 disruption with siRNA
rictor increases levels of pro-apoptotic protein Bim, decreases anti-apoptotic Bcl2 and induces apoptosis in human iPAH, but
not control PAVSMC. Collectively, our data demonstrate that mTORC2-Akt signaling is up-regulated in pulmonary hypertensive
conditions that is required for glycolytic energy metabolism, increased proliferation and survival of human iPAH and rat PH
PAVSMC and suggest that mTORC2-Akt represents novel potential therapeutic target for human PAH.
Goncharova has completed her PhD from Cardiology Research Center, Russian Academy of Sciences, and postdoctoral studies from University
of Pennsylvania Perelman School of Medicine. She is a research assistant professor in the University of Pennsylvania Perelman School of
Medicine. Her research interests are in the cellular and molecular mechanisms of smooth muscle cell remodeling as it relates to PAH, pulmonary
lymphangioleiomyomatosis, asthma and COPD. Dr. Goncharova has published 25 manuscripts in reputed journals and serves as a reviewer for
the American Journal of Respiratory Cell and Molecular Biology and the American Journal of Physiology: Lung Cellular and Molecular Physiology
Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals