Oxidized LDL promotes atherosclerosis

Oxidized LDL, low density lipoprotein that has been that has been subject to oxidation as participates in a vascular infllammatory process, is a direct risk factor for heart attacks and ischemic strokes and a more accurate predictor than 'ordinary' undamaged LDL. Research recently published in Science Signaling elucidates one of the mechanisms by which oxidized LDL promotes atherosclerosis.

Oxidized LDL promotes foam cell generation

Foam cells are the macrophages (white blood cells) filled with fat that accumulate in the build-up of atherosclerotic plaque.

"One characteristic of atherosclerosis is the accumulation of lipid-laden macrophage foam cells in the arterial wall. We have previously shown that the binding of oxidized low-density lipoprotein (oxLDL) to the scavenger receptor CD36 activates the kinase Lyn, initiating a cascade that inhibits macrophage migration and is necessary for foam cell generation."

The authors demonstrated that blocking the ion transporter Na⁺/K⁺-ATPase, a key link in this signaling chain, protects against diet-induced atherosclerosis:

"We identified the plasma membrane ion transporter Na⁺/K⁺-ATPase as a key component in the macrophage oxLDL-CD36 signaling axis. Using peritoneal macrophages isolated from Atp1a1 heterozygous or Cd36-null mice, we demonstrated that CD36 recruited an Na⁺/K⁺-ATPase–Lyn complex for Lyn activation in response to oxLDL. Macrophages deficient in the α1 Na⁺/K⁺-ATPase catalytic subunit did not respond to activation of CD36, showing attenuated oxLDL uptake and foam cell formation, and oxLDL failed to inhibit migration of these macrophages. Furthermore, Apoe-null mice, which are a model of atherosclerosis, were protected from diet-induced atherosclerosis by global deletion of a single allele encoding the α1 Na⁺/K⁺-ATPase subunit or reconstitution with macrophages that lacked an allele encoding the α1 Na⁺/K⁺-ATPase subunit. These findings identify Na⁺/K⁺-ATPase as a potential target for preventing or treating atherosclerosis."

Clinical Note

Case management of cardiovascular risk entails the measurement of oxidized LDL as a key predictive biomarker, and interval changes are important to objectively gauge the effectiveness of lifestyle and other interventions.