Durk Pearson & Sandy Shaw’s^®
Life Extension News^TM
Volume 15 No. 2 • March-April 2012

As we have discussed before, under certain conditions, HDL loses its ability to protect against atherosclerosis and actually becomes pro-atherogenic. A new paper¹ now identifies the important contribution of activated platelets (platelets that are more prone to clump together, forming blood clots) to the HDL modifications that attenuate its protective effects by, for example, inhibiting its ability to cause the efflux of cholesterol from cells and to block the oxidation of LDL.

The researchers studied C57B1/6 mice that had been genetically modified to have high-level baseline expression of the human version of sPLA2 (secretory phospho­lipase A2, released by platelets primarily in response to stimulation with proinflammatory cytokines). “... products of the sPLA2 reaction, namely lysophosphatidylcholine (LPC) and nonesterified fatty acids (NEFAs), themselves have proinflammatory effects. They are known to promote acute injury in the lung and prothrombotic and proatherogenic changes in vascular cells.”² “Increased circulating levels of sPLA2 have been linked to obesity, insulin resistance, type 2 diabetes, and metabolic syndrome, and they were found to predict coronary events in patients with cardiovascular disease (CVD).”

1. (References cited in these quotes have been deleted here)

Moreover, a high level of spontaneous and stimulated platelet activity has been identified in numerous investigations to be associated with risk factors for CVD, including tobacco smoking, hyperlipidemia, hypertension, and diabetes.¹ The authors¹ report that “[t]he results of this study demonstrate that activated platelets contribute to proatherogenic modifications of circulating LDLs and HDLs and that sPLA2 released from platelets is a key player in the process.” The study provides direct evidence that activated platelets “can modify circulating lipoproteins in vivo and that the property of platelets from distinct mouse strains is tightly related to the respective expression levels of active sPLA2.” “Earlier studies indicated that platelet-conditioned medium can modify LDLs, thus contributing to increased uptake by macrophages [part of the process of atherosclerotic plaque-forming foam cells]. In the present studies using various agonists, these oxidation-related changes were found to occur only after platelet stimulation.”¹

References

1. Blache et al. Activated platelets contribute to oxidized low-density lipoproteins and dysfunctional high-density lipoproteins through a phospho­lipase A2-dependent mechanism. FASEB J 26:927-37 (2012).