Platelet cGMP inversely correlates with age in healthy subjects

Abstract

Biochemical modifications associated with the increase in platelet activity with age are not well defined. Furthermore it is well known that the nitric oxide/cyclic 3', 5'-guanosine monophosphate (cGMP) pathway regulates platelet aggregation. The aim of the present study was to examine the relationship between platelet content of cGMP and age. 120 normal subjects, evaluating the cGMP platelet concentration, 17betaE2, IGF-I, dehydroepiandrosterone sulphate (DHEAS), insulin, plasma glucose, lipid pattern, homocysteine and PAI-I antigen, were studied. The multivariate analysis in a model with cGMP as dependent variable and with age, LDL, apolipoprotein B (ApoB), DHEAS, E2 and insulin-like growth factor (IGF)-I as independent variables shows a negative correlation between cGMP and age (p<0.01, beta=-0.388). In conclusion our data suggest that the reduced efficiency of the system constitutive nitric oxide synthase (cNOS)/guanylate cyclase represents at least one of the reasons of the increased platelet aggregability with age.

Aging of the Nitric Oxide System: Are We as Old as Our NO?

“… 53 Little is known about platelet NO responsiveness and age in unselected subjects, other than the phenomenon of age‐related reduction in platelet cGMP. 54 These parameters have not been assessed simultaneously in the past nor have they been followed up in the same cohort. Thus, the novelty of the current study is that it longitudinally evaluated changes in platelet aggregability, NO responsiveness, arterial stiffness, and ADMA concentrations in the same cohort of aging, but otherwise unselected, subjects and correlated these with one another.…”

“…Previous studies have reported a relationship between age and ADMA concentrations as well as between age and platelet hyperaggregability . Little is known about platelet NO responsiveness and age in unselected subjects, other than the phenomenon of age‐related reduction in platelet cGMP . These parameters have not been assessed simultaneously in the past nor have they been followed up in the same cohort.…”

Adenosine and blood platelets

“…Across studies in the elderly population, there is an increased concentration of clotting factors and a reduction in fibrinolytic activity in elderly populations [89,90]. Other factors that are reported to be altered with aging include: increased platelet aggregability, decreased concentration of cGMP, asymmetric phospholipid structure, reduced membrane potential of mitochondria, elevated concentrations of immunoglobulin G and fibrinogen, and impaired reactivity of platelets to thrombin [91][92][93][94]. In elderly populations, the concomitant presence of atherosclerosis complicates the distinction between age-related or vascular disease-associated changes in platelets and the clotting cascade.…”

Short‐term dehydroepiandrosterone treatment increases platelet cGMP production in elderly male subjects

“…On the other hand, NO actions are likely to be mediated by the activation of soluble guanylate cyclase that, in turn, is followed by increase in cGMP production 25 . Accordingly, we have previously demonstrated in vivo that serum DHEA‐S levels positively correlate with platelet cGMP in humans 26 …”

“…25 Accordingly, we have previously demonstrated in vivo that serum DHEA-S levels positively correlate with platelet cGMP in humans. 26 Based on the foregoing, aim of the present study was to verify whether short-term treatment with DHEA is able to positively affect platelet cGMP levels, as a marker of NO production, in male aged subjects, who are characterized by low circulating levels of DHEA-S. To this goal, in a placebo-controlled study, platelet cGMP levels as well as serum levels of DHEA, DHEA-S, IGF-1, insulin, glucose, 17 β -oestradiol (E 2 ), testosterone, PAI-1 antigen (PAI-1 Ag), homocysteine and lipid profile were evaluated before and during the administration of placebo or DHEA at physiological doses. 27…”