Function of Lipoprotein Differs in Cardiac Patients

Lipid profile blood tests indicate that high levels of "good" cholesterol (HDL cholesterol) are associated with a decreased risk of CAD, a disease of the major arterial blood vessels that is one of the major causes of heart attack and stroke.

Scientists from the University of Zurich, (Zurich, Switzerland), have investigated whether the protective potential of HDL is to be harnessed, its biological functions as well as its abundance should be considered. The investigators tested the blood from 50 patients with heart disease and 25 health individuals. They demonstrated that, in contrast to HDL from healthy subjects, HDL from patients with stable CAD or an acute coronary syndrome (HDLCAD) does not have endothelial anti-inflammatory effects and does not stimulate endothelial repair because it fails to induce endothelial nitric oxide (NO) production.

This was because in HDLCAD patients, activated endothelial lectin-like oxidized low-density lipoprotein (LDL) receptor 1 (LOX-1), triggered endothelial protein kinase isoform, (PKCβII), activation. This in turn inhibited the enzyme endothelial nitric oxide synthase (eNOS)-activating pathways and eNOS-dependent NO production. They identified reduced HDL-associated paraoxonase 1 (PON1) activity as one molecular mechanism leading to the generation of HDL with endothelial PKCβII-activating properties, at least in part due to increased formation of malondialdehyde in HDL.

The authors concluded that in patients with CAD, HDL gains endothelial LOX-1 and thereby PKCβII-activating properties due to reduced HDL-associated PON1 activity, and that this leads to inhibition of eNOS-activation and the subsequent loss of the endothelial anti-inflammatory and endothelial repair-stimulating effects of HDL. These findings support the concept that the biological functions of HDL in addition to its plasma levels may have to be taken into account to assess the cardiovascular effects of HDL-raising therapies in patients with CAD. The article was published on July 1, 2011 in the Journal of Clinical Investigation.

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