Molecular and Genetic Cardiovascular Pathophysiology
Cardiovascular disease (CVD) is the main health and socio-economic problem worldwide, in part due to the progressive aging that the world population is experiencing. Atherosclerosis and heart failure contribute significantly to CVD-related morbimortality in the elderly. These anomalies and the aging process are much accelerated in Hutchinson-Gilford progeria syndrome (HGPS), a rare genetic disorder (prevalence about 1 in 18 million) caused by the expression of progerin, a mutant form of lamin A. The most serious aspect of HGPS is extensive atherosclerosis and cardiac electrophysiological alterations which are associated with early death (average lifespan: 14.6 yr), predominantly from myocardial infarction or stroke. Progerin is also expressed at low level in aged tissues of non-HGPS individuals, suggesting a role in normal aging. Understanding how progerin causes CVD and premature aging may therefore shed light on normal aging.
Our research currently focuses on:
- Generating and characterizing new preclinical models (mouse and pig) to study the role of A-type lamins and progerin in CVD and aging.
- Identifying systemic and tissue-specific factors and investigating the relative contribution of different cell types to the development of HGPS and associated CVD.
- Developing and testing in preclinical models new therapies to treat CVD associated to physiological and premature aging.
- Investigating the role of leukocyte telomere shortening in atherosclerosis development and its possible interaction with clonal hematopoiesis associated to somatic mutations.