HMG-CoA reductase enzyme could add to plaque instability
MedWire News: South-Korean researchers have discovered that hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase may contribute to coronary artery plaque instability, which could help to explain some early benefits of statin therapy.
They found HMG-CoA reductase in coronary atherosclerotic plaques, and showed that levels were greater in plaques that were unstable. Immunohistochemical staining revealed that cells immunopositive for HMG-CoA reductase were mostly macrophages.
The researchers say: "These findings support a potential role for HMG-CoA reductase in the pathogenesis of acute coronary syndromes (ACS) and may help to explain the early benefits of statin therapy in patients with ACS."
The team from Seoul studied coronary atherectomy tissue retrieved from 22 patients with unstable angina and 21 patients with stable angina. All had undergone directional coronary atherectomy for de novo coronary lesions.
The specimens were stained with hematoxyline-eosin and incubated with antibodies specific to HMG-CoA reductase, macrophages, smooth muscle cells, and endothelial cells.
Baseline characteristics were similar between the two groups of patients, report Seung-Jung Park (University of Ulsan) and colleagues in the journal Heart.
However, immunopositive areas of HMG-CoA reductase, macrophages, endothelial cells, and thrombi were significantly greater among individuals with unstable than stable angina.
In contrast, the immunopositive area of smooth muscle cells did not significantly differ between the two groups. Macrophage-positive areas correlated well with areas of HMG-CoA reductase only in patients with unstable angina.
The researchers say: "These findings suggest that local HMG-CoA reductase is functionally active, and lesion macrophages in unstable angina more actively produce HMG-CoA reductase than in stable angina.
"Statin therapy may rapidly inhibit vascular HMG-CoA reductase and attenuate macrophage function by dampening of plaque inflammation, subsequently decreasing the risk of plaque embolization after percutaneous coronary intervention to unstable plaque.
"In contrast, the positive areas for macrophage and HMG-CoA reductase were smaller in stable plaque than in unstable plaque. These findings may account for the potentially different effects of statins according to clinical presentation."
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By Anita Wilkinson