Roles of lysophosphatidic acid in cardiovascular physiology and disease

The bioactive lipid mediator lysophosphatidic acid (LPA) exerts a range of effects on the cardiovasculature that suggest a role in a variety of critical cardiovascular functions and clinically important cardiovascular diseases. LPA is an activator of platelets from a majority of human donors identifying a possible role as a regulator of acute thrombosis and platelet function in atherogenesis and vascular injury responses. Of particular interest in this context, LPA is an effective phenotypic modulator of vascular smooth muscle cells promoting the de-differentiation, proliferation and migration of these cells that are required for the development of intimal hyperplasia. Exogenous administration of LPA results in acute and systemic changes in blood pressure in different animal species, suggesting a role for LPA in both normal blood pressure regulation and hypertension. Advances in our understanding of the molecular machinery responsible for the synthesis, actions and inactivation of LPA now promise to provide the tools required to define the role of LPA in cardiovascular physiology and disease. In this review we discuss aspects of LPA signaling in the cardiovasculature focusing on recent advances and attempting to highlight presently unresolved issues and promising avenues for further investigation.     

Dietary hydroxy fatty acids are absorbed in humans: implications for the measurement of 'oxidative stress' in vivo.

Lipid peroxidation products formed in vivo or originating from the diet may lead to atherosclerosis. However, little is known about the absorption of these products in man. We studied the absorption of fat (30 g) containing 14-15 mg [U-13C]-labeled hydroxy or dihydroxy triglycerides in two groups of six apparently healthy women aged 40 +/- 2 years. Post-prandial 13C-labeled hydroxy fatty acid concentration increased in a pattern somewhat different from that of plasma triglycerides, with peak levels being reached between 4 and 6 h. However, the amount of 13C-labeled oxidized fat absorbed (area under the curve of plasma concentrations from 0 to 8 h) was related to that of plasma triglycerides: 13C hydroxy vs TG (r = 0.88, p <.02), and 13C dihydroxy vs TG (r = 0.85, p <.05). 13C monohydroxy triglycerides appeared to be absorbed to a greater extent than those of 13C dihydroxy triglycerides. Although low levels of 13C hydroxy lipids could be detected in fasting plasma after 24 h, concentrations were very low. Dietary lipid oxidation products are absorbed. The measurement of hydroxy fatty acids in plasma total lipids may not be a valid marker of lipid peroxidation in vivo when subjects are not fasting.