The development of atherosclerotic
cardiovascular disease is a common comorbidity in patients with the
metabolic syndrome, a concurrence of cardiovascular risk factors in one individual. While multiple
growth factors and
adipokines are identified in atherosclerotic lesions, as well as
neurotrophins implicated in both cardiac
ischemia and
lipid and
glucose metabolism, the potential role of
neurotrophins in human
coronary atherosclerosis and in the
metabolic syndrome still remains to be elucidated. Here we describe and discuss our results that represent a novel attempt to study the cardiovascular and metabolic biology of
nerve growth factor (
NGF),
brain-derived neurotrophic factor (
BDNF) and mast cells (MC). The local amount of
NGF, the immunolocalization of
p75 neurotrophin receptor (p75NTR) and the number of MC were correlatively examined in coronary vascular wall and in the surrounding subepicardial adipose tissue, obtained from autopsy cases in humans with advanced
coronary atherosclerosis. We also analyzed the plasma levels of
NGF,
BDNF and
leptin and the number of MC in biopsies from abdominal subcutaneous adipose tissue in patients with a severe form of the
metabolic syndrome. The results demonstrate that
NGF levels are decreased in atherosclerotic coronary vascular tissue but increased in the subepicardial adipose tissue, whereas both tissues express a greater number of MC and a stronger p75NTR immunoreactivity, compared to controls.
Metabolic syndrome patients display a significant hyponeurotrophinemia and an increased number of adipose MC; the later correlates with elevated plasma
leptin levels. In effect, we provide the first evidence for (i) an altered presence of
NGF, p75NTR and MC in both coronary vascular and subepicardial adipose tissue in human
coronary atherosclerosis, and (ii) a significant decrease in plasma
NGF and
BDNF levels and an elevated amount of plasma
leptin and adipose MC in
metabolic syndrome patients. Together our findings suggest that neuroimmune mediators such as
NGF,
BDNF,
leptin and MC may be involved in the development of
cardiovascular disease and related disorders.