Title:Benefit of SERCA2a Gene Transfer to Vascular Endothelial and Smooth Muscle Cells: A New Aspect in Therapy of Cardiovascular Diseases
Volume: 11
Issue: 4
Author(s): Larissa Lipskaia, Lahouaria Hadri, Jose J. Lopez, Roger J. Hajjar and Regis Bobe
Affiliation:
Keywords:
Cardiovascular disease, endothelial cells, gene therapy, SERCA2a, vascular smooth muscle cells.
Abstract: Despite the great progress in cardiovascular health and clinical care along with marked decline in morbidity
and mortality, cardiovascular diseases remain the leading causes of death and disability in the developed world. New
therapeutic approaches, targeting not only systematic but also causal dysfunction, are ultimately needed to provide a valuable
alternative for treatment of complex cardiovascular diseases. In heart failure, there are currently a number of trials
that have been either completed or are ongoing targeting the sarcoplasmic reticulum calcium ATPase pump (SERCA2a)
gene transfer in the context of heart failure. Recently, a phase 2 trial was completed, demonstrating safety and suggested
benefit of adeno-associated virus type 1/SERCA2a gene transfer in advanced heart failure, supporting larger confirmatory
trials. The experimental and clinical data suggest that, when administrated through perfusion, virus vector carrying
SERCA2a can also transduce vascular endothelial and smooth muscle cells (EC and SMC) thereby improving the clinical
benefit of gene therapy. Indeed, recent advances in understanding the molecular basis of vascular dysfunction point towards
a reduction of sarcoplasmic reticulum Ca2+ uptake and an impairment of Ca2+ cycling in vascular EC and SMC
from patients and preclinical models with cardiac diseases or with cardiovascular risk factors such as diabetes, hypercholesterolemia,
coronary artery diseases, as well as other conditions such as pulmonary hypertension. In recent years, several
studies have established that SERCA2a gene-based therapy could be an efficient option to treat vascular dysfunction. This
review focuses on the recent finding showing the beneficial effects of SERCA2a gene transfer in vascular EC and SMC.
