Mechanisms of vascular aging: What can we learn from Hutchinson-Gilford progeria syndrome?

Aging is the main risk factor for cardiovascular disease (CVD). The increased prevalence of CVD is partly due to the global increase in life expectancy. In this context, it is essential to identify the mechanisms by which aging induces CVD, with the ultimate aim of reducing its incidence. Both atherosclerosis and heart failure significantly contribute to age-associated CVD morbidity and mortality. Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder caused by the synthesis of progerin, which is noted for accelerated aging and CVD. This mutant form of prelamin A induces generalised atherosclerosis, vascular calcification, and cardiac electrophysiological abnormalities, leading to premature aging and death, mainly due to myocardial infarction and stroke. This review discusses the main vascular structural and functional abnormalities during physiological and premature aging, as well as the mechanisms involved in the exacerbated CVD and accelerated aging induced by the accumulation of progerin and prelamin A. Both proteins are expressed in non-HGPS individuals, and physiological aging shares many features of progeria. Research into HGPS could therefore shed light on novel mechanisms involved in the physiological aging of the cardiovascular system.El trabajo desarrollado en el laboratorio de V. A. se ha financiado por el Ministerio de Economía, Industria y Competitividad (MEIC; SAF2016-79490-R) y el Instituto de Salud Carlos III (ISCIII) (RD12/0042/0028 y AC16/00091), con cofinanciación del Fondo Europeo de Desarrollo Regional (FEDER), de la Fundació Marató de TV3 (122/C/2015) y la Progeria Research Fundation (Established Investigator Award 2014-52). El CIBER de Enfermedades Cardiovasculares es una iniciativa del ISCIII. L. C. recibió una ayuda del programa de becas posdoctorales Jordi Soler de la Red de Investigación Cardiovascular (ISCIII) y M. R. H., una ayuda predoctoral del programa FPI del MEIC (BES-2011-043938). El CNIC cuenta con el apoyo del MEIC y de la Fundación Pro-CNIC y ha sido acreditado como Centro de Excelencia Severo Ochoa (MEIC SEV-2015-0505).S