Enhanced platelet activation by prolactin in patients with ischemic stroke

Abstract

Prolactin and leptin are newly recognised platelet co-stimulators due to potentiation of ADP-induced platelet aggregation. Elevated leptin levels have recently been found to be a risk factor for ischemic stroke in both men and women, and especially in combination with increased blood pressure for hemorrhagic stroke in men. Until now an association between hyperprolactinemia and ischemic stroke has not been investigated systematically. We determined plasma prolactin and leptin levels as well as platelet P-selectin expression in 36 patients with ischemic stroke or transient ischemic attack and detected a significant correlation between increased prolactin values and enhanced ADP stimulated P-selectin expression on platelets. In contrast, no correlation of leptin values with platelet P-selectin expression was found. Next we determined plasma prolactin and leptin as well as acquired and congenital risk factors of thrombophilia in patients with first-ever non-hemorrhagic stroke with or without atrial fibrillation. Excluding patients with such preexisting risk factors, 21 patients with and 59 patients without atrial fibrillation were identified. Patients without atrial fibrillation revealed significantly higher plasma prolactin levels than patients with atrial fibrillation. Furthermore, the influence of aspirin or clopidogrel on prolactin stimulated P-selectin expression in vitro was tested, showing that aspirin was without effect, whereas clopidogrel significantly inhibited platelet P-selectin expression. In conclusion, hyperprolactinemia might be a novel risk factor for stroke mediating its thrombogenic effect through enhanced platelet reactivity, and this might correspond to a higher efficacy of antiplatelet combination therapy with clopidogrel compared to aspirin therapy alone.

Assessment of serum prolactin levels in acute myocardial infarction: The role of pharmacotherapy

“…As well, prolactin induces expression of P-selectin in the platelet and augment of adenosine diphosphate-induced platelet aggregation leading to thrombosis in acute coronary syndromes mainly in acute MI, also there was an association between high prolactin level and stroke,[ 26 ] which corresponded with our findings that show a potential link between prolactin serum level and incidence of acute MI.…”

“…[ 25 ] Therefore, prolactin was implicated in the inflammatory changes that occur to acute attack of MI, and the correlation between high prolactin and CRP level is well documented. [ 26 ]…”

A Network Pharmacology Approach to Investigate the Active Compounds and Mechanisms of Musk for Ischemic Stroke

“…Moreover, prolactin is a cofactor for platelet activation [ 70 ]. Hyperprolactinemia may be part of the risk factors for stroke, which mediates thrombosis by enhancing platelet reactivity [ 71 ]. Neurotrophins family, including nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3, play an important role in the repair of neural tissue damage.…”

The Mediterranean Diet Benefit on Cardiovascular Hemodynamics and Erectile Function in Chronic Heart Failure Male Patients by Decoding Central and Peripheral Vessel Rheology

“…Regarding the role of prolactin in heart and vessels diseases, it is increasingly recognized that this hormone is involved in cardiovascular pathophysiology, exerting pleiotropic unfavourable haemodynamic and pro-atherosclerotic actions, raising overall cardiovascular risk [6,9,28,29]. Hyperprolactinaemia has been related to endothelial dysfunction and arterial stiffness [3], low-grade inflammation [2,5], increased thromboembolic risk [7] and dyslipidemia [2]. For example, plasma prolactin levels are elevated in conditions such as the acute phase of myocardial infarction, ischemic stroke, and transient ischemic attack, hypertension and preeclampsia, while evidence suggests a causative role of prolactin in postpartum cardiomyopathy [5][6][7][8]28].…”

“…Erectile dysfunction (ED) is strongly correlated with sex-hormones and prolactin levels, and has been used as a proxy of quality of life. ED has been related with hemodynamic status and seems to display peripheral vessel rheology, even in patients with atherosclerosis and CHF, while the role of serum prolactin role is still debated in CHF mechanisms is still under consideration [2][3][4][5][6][7][8][9].…”