New Insights for BPIFB4 in Cardiovascular Therapy

Int J Mol Sci. 2020 Sep 28;21(19):7163. doi: 10.3390/ijms21197163.

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.

Keywords: BPIFB4; aging; cardiovascular disease.

Publication types

  • Review

MeSH terms

  • Adaptive Immunity
  • Age Factors
  • Animals
  • Atherosclerosis / genetics*
  • Atherosclerosis / immunology
  • Atherosclerosis / prevention & control
  • Diabetic Cardiomyopathies / genetics*
  • Diabetic Cardiomyopathies / immunology
  • Diabetic Cardiomyopathies / prevention & control
  • Frailty / genetics*
  • Frailty / immunology
  • Frailty / prevention & control
  • Gene Expression Regulation, Developmental / immunology
  • Genetic Therapy / methods
  • Humans
  • Hypertension / genetics*
  • Hypertension / immunology
  • Hypertension / prevention & control
  • Immunity, Innate
  • Immunosenescence / genetics*
  • Intercellular Signaling Peptides and Proteins
  • Longevity / genetics*
  • Longevity / immunology
  • Mice
  • Nitric Oxide Synthase Type III / genetics
  • Nitric Oxide Synthase Type III / immunology
  • Phosphoproteins / genetics*
  • Phosphoproteins / immunology
  • Protein Isoforms / genetics
  • Protein Isoforms / immunology
  • Risk Factors

Substances

  • BPIFB4 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Phosphoproteins
  • Protein Isoforms
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III