Abstract
Aging is the major risk factor per se for the development of cardiovascular diseases. The senescence of the endothelial cells (ECs) that line the lumen of blood vessels is the cellular basis for these age-dependent vascular pathologies, including atherosclerosis and hypertension. During their lifespan, ECs may reach a stage of senescence by two different pathways; a replicative one derived from their preprogrammed finite number of cell divisions; and one induced by stress stimuli. Also, certain physiological stimuli, such as transforming growth factor-β, are able to modulate cellular senescence. Currently, the cellular aging process is being widely studied to identify novel molecular markers whose changes correlate with senescence. This review focuses on the regulation of alternative splicing mediated by the serine–arginine splicing factor 1 (SRSF1, or ASF/SF2) during endothelial senescence, a process that is associated with a differential subcellular localization of SRSF1, which typically exhibits a scattered distribution throughout the cytoplasm. Based on its senescence-dependent involvement in alternative splicing, we postulate that SRSF1 is a key marker of EC senescence, regulating the expression of alternative isoforms of target genes such as endoglin (ENG), vascular endothelial growth factor A (VEGFA), tissue factor (T3), or lamin A (LMNA) that integrate in a common molecular senescence program.
Highlights
It is well established that vascular physiology declines with aging due to the impairment of endothelial functions
This endothelial dysfunction is fairly evidenced by the stiffening of blood vessels that fail to control the dilatory responses associated with hypertension (Versari et al, 2009), and by a pro-inflammatory state of the endothelial microenvironment that favors the development of atherosclerosis (Erusalimsky, 2009)
There is growing interest in the molecular components that orchestrate the modulation of alternative splicing events in senescent endothelial cells (ECs)
Summary
It is well established that vascular physiology declines with aging due to the impairment of endothelial functions. Processes including vasculogenesis and angiogenesis require repeated division of ECs, but in adults these cells are in a quiescent state and divide only occasionally (Conway and Carmeliet, 2004; Semenza, 2007; Carmeliet and Jain, 2011) At this latter stage ECs remain highly responsive to mechanical stimuli, such as shear stress and injuries, as well as to chemical signals, including hypoxia, cytokines, and growth factors, among others. During vascular remodeling or upon angiogenic stimulation, ECs actively proliferate, but progressively lose their capacity to divide, reaching the stage of replicative senescence This process involves telomere shortening until the cells reach the so-called Hayflick’s limit (Brandes et al, 2005), that renders cell division impossible, constituting a mechanism to prevent genomic instability and the development of cancer (Shay and Wright, 2007).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
