Chronic inflammatory disorders and accelerated atherosclerosis: chronic kidney disease.

Kaveh D Navab, Omeed Elboudwarej, Mackena Gharif, Jeryl Yu, Susan Y Hama, Sheila Safarpour, Greg P Hough, Ladan Vakili, Srinivasa T Reddy, Mohamad Navab, Nosratola D Vaziri

David Geffen School of Medicine, 10833 Le Conte Ave., University of California Los Angeles, CA 90095, USA. KavehNavab@mednet.ucla.edu

Current pharmaceutical design 2011

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Increasing evidence points to the fact that plasma HDL cholesterol levels do not always accurately predict HDL function including reverse cholesterol transport and modulation of inflammation. These functions appear to have evolved as part of our innate immune system. HDL is anti inflammatory in healthy individuals in the absence of systemic oxidative stress and inflammation. In those with chronic illnesses such as renal failure however, HDL may become dysfunctional and actually promote inflammation. HDL may be thought of as a shuttle whose size can be estimated by HDL cholesterol levels. The content of the shuttle however, is what determines the anti inflammatory potential of HDL and can change from one, supporting reverse cholesterol transport to one that is less efficient in carrying out this function. Chronic kidney disease (CKD), and inflammatory disorder, is associated with development of accelerated atherosclerosis and premature death from coronary artery disease (CAD). Patients with CKD present with dyslipidemia, oxidative stress and systemic inflammation. Among the abnormalities in lipid metabolism in these patients is reduced levels and protective capacity of HDL. Recent studies have shown that HDL from patients with end stage renal disease is not capable of preventing LDL oxidation and that it induces monocyte migration in artery wall model systems. Treatment of plasma from these patients, with an HDL mimetic peptide improved the anti inflammatory properties of patient's HDL and made LDL more resistant to oxidative modification. Animal models of kidney disease also had proinflammatory HDL and treatment with the peptide mimetic improved markers of inflammation and anti inflammatory capacity of HDL. Whether HDL mimetic peptides will have therapeutic benefit in patients with renal failure will have to be determined in clinical studies.

Citation

Kaveh D Navab, Omeed Elboudwarej, Mackena Gharif, Jeryl Yu, Susan Y Hama, Sheila Safarpour, Greg P Hough, Ladan Vakili, Srinivasa T Reddy, Mohamad Navab, Nosratola D Vaziri. Chronic inflammatory disorders and accelerated atherosclerosis: chronic kidney disease. Current pharmaceutical design. 2011;17(1):17-20