Abstract
Aging is the most relevant risk factor for cardiovascular diseases which are the main cause of mortality in industrialized countries. In this context, there is a progressive loss of cardiovascular homeostasis that translates in illness and death. The study of long living individuals (LLIs), which show compression of morbidity toward the end of their life, is a valuable approach to find the key to delay aging and postpone associate cardiovascular events. A contribution to the age-related decline of cardiovascular system (CVS) comes from the immune system; indeed, it is dysfunctional during aging, a process described as immunosenescence and comprises the combination of several processes overpowering both innate and adaptative immune system. We have recently discovered a longevity-associated variant (LAV) in bactericidal/permeability-increasing fold-containing family B member 4 (BPIFB4), which is a secreted protein able to enhance endothelial function through endothelial nitric oxide synthase (eNOS) activation and capable to protect from hypertension, atherosclerosis, diabetic cardiopathy, frailty, and inflammaging. Here, we sum up the state of the art of the mechanisms involved in the main pathological processes related to CVD (atherosclerosis, aging, diabetic cardiopathy, and frailty) and shed light on the therapeutic effects of LAV-BPIFB4 in these contexts.
Highlights
Cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity of the over 65 years old population
We summarize and discuss the state of the art of the mechanisms involved in atherosclerosis (ATS), aging, and frailty, as relevant orchestrators of CVD, and the effects of longevity-associated variant (LAV)-Bactericidal/permeability-increasing fold-containing family B member 4 (BPIFB4) in these contexts
Malavolta et al showed that BPIFB4 haplotypes co-segregate with frailty and, subsequently, in order to obtain functional evidence of this association, gene therapy with LAV-BPIFB4 was used in a murine model of aging to counteract frailty
Summary
Cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity of the over 65 years old population. Progressive aging of the population associates with frailty state, representing the most relevant risk factor in CVDs. Aging is a consequence of the increase of the life expectancy. Bactericidal/permeability-increasing fold-containing family B member 4 (BPIFB4) is a secreted protein that has been identified on a genome wide association study, in an Italian set of long-living individuals (LLIs) and controls. This association was validated in two independent populations from Germany and the USA, that showed consistent enrichment in LLIs under recessive model of the minor allele rs2070325 (I229V) of BPIFB4. The following keywords were used to generate a search: BPIFB4, aging, frailty, atherosclerosis, type 2 diabetes, and inflammaging
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