Patients with risk factors have higher plasma levels of lysophosphatidic acid: a promising surrogate marker for blood platelet activation.

Although basic medical studies have shown that lysophosphatidic acid (LPA) has an important relationship to activated blood platelets, we know little about this from clinical experience. This pilot study examined plasma LPA levels in patients with a risk of thrombotic events and evaluated the effects of aspirin on plasma LPA levels. In this basically cross-sectional study, we recruited 1352 patients with either hypertension or hyperlipidemia and 670 controls without any risk factors. Patients with risk factors had significantly higher plasma LPA levels than controls, the mean of LPA = 3.12 ±â€Š2.24 vs. 2.57 ±â€Š1.96 µmol/l, P < 0.001. The patients who had been taking aspirin had relatively lower plasma LPA levels compared with those who did not take aspirin, χ = 43.8, odds ratio (OR) [95% confidence interval (CI)] = 2.76 (2.03-3.75). For the hypertension group, χ = 23.1, OR (95% CI) = 3.44 (2.03-5.82), P < 0.001; for the hyperlipidemia group, χ = 22.9, OR (95% CI) = 2.53 (1.72-3.74), P < 0.001. Patients with a risk factor had higher plasma LPA levels compared with controls. Administration of aspirin may decrease elevated plasma LPA levels. This pilot clinical observation indicates that plasma LPA is worth to be studied further.

[A preliminary study on the correlation between clinical makers with the length of patients' hypertension history].

OBJECTIVE: To investigate the correlation between length of hypertension history with plasma level of A Phospholipids Component with the Similar Solubility of Lyso-Phosphatidic Acid (APCSSLPA or briefly AP). So that to farther understand the changes accompanied with prolongation of hypertension history. METHODS: This is a small cross-sectional study. 170 patients with primary hypertension and 79 normal controls without hypertension history were enrolled. The lengths of case history were recorded and compared with their plasma levels of AP. Similar study were also conducted on other 11 clinical makers as references. RESULTS: AP correlated significantly with the length of hypertension history. Correlation coefficient beta is 0.186, P = 0.015. But AP did not correlated significantly with systolic or diastolic pressure of patients. The age of patients did not correlated with AP either (beta = 0.027, P = 0.71). The patient's number with middle or high level of AP was significantly larger in the group in which hypertension history was 10 years or more, than in the group in which hypertension history was less then 10 years. chi(2) = 6.51, P = 0.012. OR = 2.444, 95%CI = 1.219 - 4.903. However, lysophosphatidic acid and other 10 bio-makers which often be used in cerebrovascular and cardiovascular diseases, such as blood lipid, blood sugar, different kinds of lipoprotein and D-dimer etc. did not correlated significantly with hypertension history. CONCLUSION: Comparing with 11 clinical makers, AP was the only one correlated with the length of hypertension history. Our findings suggest: the prolongation of hypertension history may accompanied with increased oxidative damages. The patients with prolonged hypertension history should prevent this possible threaten. Furthermore, AP is a very promising marker with unique worth in cardiovascular and cerebrovascular diseases.

Influence of acetylsalicylate on plasma lysophosphatidic acid level in patients with ischemic cerebral vascular diseases.

BACKGROUND AND PURPOSE: Lysophosphatidic acid (LPA) is released from activated platelets. Acetylsalicylate (aspirin) is the most commonly used antiplatelet drug. The purpose of this study is to observe whether treatment with acetylsalicylate decreases the LPA level in patients with ischemic cerebrovascular diseases. METHODS: We performed a study examining LPA level in fresh plasma in cases and controls enrolled in the LPA and Stroke Prevention Study. Level of LPA was assayed by measuring its inorganic phosphorus after separation by chromatography. RESULTS: An elevated LPA level was seen in cases (n = 254) with ischemic cerebrovascular disease (3.11+/- 1.55 micromol/l) compared with 136 healthy controls (1.77 +/- 1.04 micromol/l) (p < 0.001). Administration of aspirin (100 mg q.d.) for 1 month significantly lowered LPA level in patients (n = 142) (2.41 +/- 1.03 mu mol/l) compared with that before taking acetylsalicylate (4.06 +/- 1.03 micromol/l) (p < 0.001). However, the LPA level in patients (n = 36) who stopped acetylsalicylate after taking it for 1 month was re-elevated. Before and after taking acetylsalicylate for 1 month, their LPA levels were 4.23 +/- 1.15 and 1.93 +/- 0.85 micromol/l, respectively. After 1 month withdrawal, level was 3.90 +/- 1.09 micromol/l (p < 0.001 compared that before taking acetylsalicylate). CONCLUSION: Our findings support a close association between increased plasma LPA level and platelet activation. Acetylsalicylate could decrease plasma LPA levels, which may be used as a mechanism for acetylsalicylate in the prevention of ischemic stroke.

[Lysophosphatidic acid activates L-arginine/nitric oxide pathway of platelets in rats].

OBJECTIVE: To investigate the mechanism of platelet function caused by Lysophosphatidic acid (LPA), by observing the change of the L-arginine/nitric oxide synthase/nitric oxide (L-Arg/NOS/NO) pathway of platelet in rats. METHODS: LPA (10(-6), 10(-5) and 5x10(-5) mol/L) was administrated in rats and incubated for 30 and 60 minutes. The nitrite production was measured by Greiss assay; NOS activities and L-arginine transportation were detected by isotope tracer method and intracellular [Ca(2+)]i changes by fluorescent probe. RESULTS: LPA increased NO release by 35% and 56%, after incubating for 30 and 60 minutes, respectively. LPA (10(-6), 10(-5)aand 5x10(-5) mol/L) enhanced the NO productions of platelets in a concentration-dependent manner (P<0.01). EC(50) was 17.8 micromol/L, and 95% CI was 13.3-24.2 micromol/L, involved in the physiological concentration of LPA in plasma (P<0.01). Simultaneously, different doses of LPA increased NOS activities and L-arginine uptake in a dose-dependent manner (P<0.01). In this study, LPA (50 micromol/L) increased the intracellular free calcium ion concentration ([Ca(2+)]i, P<0.01), after incubating for 30 and 60 minutes. Pre-treated with NOS inhibitor-L-NAME for 20 minutes, LPA obviously enhanced the effects by 20% and 32% respectively (P<0.01). On the contrary, pre-treated with L-arginine (200 micromol/L) for the same times obviously reduced the effects by 14% and 18% respectively (P<0.01). CONCLUSION: LPA increased NO release by enhancing L-arginine uptake and NOS activities, up-regulating L-arginine/NOS/NO pathway in platelets of rats.

Effects of adrenomedullin on cell proliferation in rat adventitia induced by lysophosphatidic acid.

Lysophosphatidic acid (LPA) is a bioactive phospholipid having growth factor-like activity on fibroblasts and is involved in cardiovascular diseases such as hypertension and heart failure by inducing vascular remodeling, characterized by fibroblast proliferation and migration in adventitia. Among various bioactive factors that LPA works with, adrenomedullin (ADM) is a multiple functional peptide with an important cytoprotective effect against cardiovascular damage. We studied rat aortic adventitia to explore the possible paracrine/autocrine interaction between endogenous ADM and LPA. LPA stimulation of the adventitia to secrete ADM and express its mRNA was concentration dependent. ADM inhibited LPA-induced proliferation in adventitial cells and attenuated the activity of mitogen-activated protein kinase (MAPK) stimulated by LPA. In contrast, treatment with specific antagonists of the ADM receptor potentiated the LPA-induced proliferation in adventitial cells. We concluded that LPA stimulates the adventitia to produce and secrete ADM, which in turn regulates the vascular biological effects of LPA.