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:

  1. Generating and characterizing new preclinical models (mouse and pig) to study the role of A-type lamins and progerin in CVD and aging.
  2. Identifying systemic and tissue-specific factors and investigating the relative contribution of different cell types to the development of HGPS and associated CVD.
  3. Developing and testing in preclinical models new therapies to treat CVD associated to physiological and premature aging.
  4. Investigating the role of leukocyte telomere shortening in atherosclerosis development and its possible interaction with clonal hematopoiesis associated to somatic mutations.