Effect of parathyroid-hormone-related protein on human platelet activation

Abstract

Evidence suggests that PTHrP [PTH (parathyroid hormone)-related protein] can act as an inflammatory mediator in several pathological settings including cardiovascular disease. The aim of the present study was to determine whether PTHrP might be involved in human platelet activation. We used a turbidimetric method to determine platelet aggregation. The expression of PTH1R (PTH type 1 receptor) in human platelets was analysed by Western blot and flow cytometry analyses. PTHrP-(1-36) (10(-7) mol/l) by itself failed to modify the activation of platelets. However, it significantly enhanced ADP-induced platelet activation, and also increased the ability of other agonists (thrombin, collagen and arachidonic acid) to induce platelet aggregation. H89 (10(-6) mol/l) and 25 x 10(-6) mol/l Rp-cAMPS (adenosine 3',5'-cyclic monophosphorothioate Rp-isomer), two protein kinase A inhibitors, and 25 x 10(-9) mol/l bisindolylmaleimide I, a protein kinase C inhibitor, partially decreased the enhancing effect of PTHrP-(1-36) on ADP-induced platelet activation. Meanwhile, 10(-6) mol/l PTHrP-(7-34), a PTH1R antagonist, as well as 10(-5) mol/l PD098059, a MAPK (mitogen-activated protein kinase) inhibitor, or a farnesyltransferase inhibitor abolished this effect of PTHrP-(1-36). Moreover, 10(-7) mol/l PTHrP-(1-36) increased (2-fold over control) MAPK activation in human platelets. PTH1R was detected in platelets, and the number of platelets expressing it on their surface in patients during AMI (acute myocardial infarction) was not different from that in a group of patients with similar cardiovascular risk factors without AMI. Western blot analysis showed that total PTH1R protein levels were markedly higher in platelets from control than those from AMI patients. PTH1R was found in plasma, where its levels were increased in AMI patients compared with controls. In conclusion, human platelets express the PTH1R. PTHrP can interact with this receptor to enhance human platelet activation induced by several agonists through a MAPK-dependent mechanism.

Plasma desmoplakin I biomarker of vascular recurrence after ischemic stroke

“…Ten micrograms of total plasma protein from each of the 134 included patients were loaded onto a nitrocellulose membrane as reported (Ortega et al. 2007).…”

“…Ten micrograms of total plasma protein from each of the 134 included patients were loaded onto a nitrocellulose membrane as reported (Ortega et al 2007). Nitrocellulose membrane was blocked with 5% (w/v) bovine serum albumin, incubated with a monoclonal desmoplakin antibody [Desmoplakin I/II (C-20); sc-18086, Santa Cruz Biotechnology, Inc. , Santa Cruz, CA, USA; dilution 1 : 1000] that recognizes the C-terminus of human desmoplakin, and incubated with a peroxidase-conjugated goat anti-mouse IgG and developed using enhancing chemiluminiscence reagents (ECL; GE Healthcare, Little Chalfont Buckinghamshire, UK).…”

To evaluate the role of plasma vitamin D level as a prognostic marker and its relation to in-hospital complications in patients with acute coronary syndrome

“…9,[15][16][17][30][31][32] Additionally, vitamin D deficiency has been associated with endothelial dysfunction, which is, in turn, linked to an increased risk of cardiovascular events. 33,34 In particular, the endothelium mediates vascular tone control, platelet aggregation, endothelium permeability, and neoangiogenesis; thus, its dysfunction may exacerbate coronary thrombosis and vasoconstriction occurring during ACS.…”

“…Notably, vitamin D has been demonstrated to suppress the reninangiotensin system and to affect endothelial function, inflammatory processes, platelet function, insulin resistance, and blood pressure. 3,[14][15][16] All these effects are relevant during ACS, and related to patients' clinical course. Moreover, low levels of vitamin D have been associated with ventricular dysfunction and cardiac remodeling after ACS, and with heart failure mortality and sudden cardiac death.…”

Prevalence of Vitamin D Deficiency in Acute Coronary Syndrome in a Tertiary Care Hospital, Maharashtra, India

“…Notably, vitamin D has been demonstrated to suppress the reninangiotensin system and to affect endothelial function, inflammatory processes, platelet function, insulin resistance and blood pressure. [13,[24][25][26][27] All these effects are relevant during ACS and related to patient's clinical course. Moreover, low levels of vitamin D have been associated with ventricular dysfunction and cardiac remodeling after ACS and with heart failure mortality and sudden cardiac death.…”