The Effect of PCSK9 Inhibition on the Stabilization of Atherosclerotic Plaque Determined by Biochemical and Diagnostic Imaging Methods

Abstract

Atherosclerosis is a multifactorial, progressive, chronic inflammatory disease. Ultrasound and magnetic resonance imaging are the most accurate predictors of atherosclerotic plaque instability (MRI). Cytokines such as osteopontin, osteoprotegerin, and metalloproteinase 9 could be used as the most recent markers to identify and track the efficacy of anti-atherosclerotic therapy. Patients with USG and MRI-verified unstable atherosclerotic plaque were included in the study. Biomarker concentrations were measured and compared before and after PCSK9 inhibitor therapy. Additionally, concentrations prior to treatment were correlated with MRI images of the carotid artery. After treatment with alirocumab, the concentrations of MMP-9 (p < 0.01) and OPN, OPG (p < 0.05) decreased significantly. Furthermore, the results of OPN, OPG, and MMP 9 varied significantly depending on the type of atherosclerotic plaque in the MRI assay. In stable atherosclerotic plaques, the concentrations of OPN and OPG were greater (p < 0.01), whereas the concentration of MMP9 correlated with the instability of the plaque (p < 0.05). We demonstrated, probably for the first time, that alirocumab therapy significantly decreased the serum concentration of atherosclerotic plaque markers. In addition, we demonstrated the relationship between the type of atherosclerotic plaque as determined by carotid MRI and the concentration of these markers.

The Anti-atherosclerotic Effects of Endothelin Receptor Antagonist, Bosentan, in Combination with Atorvastatin – an Experimental Study

“…Our study provides a novel anti-atherosclerotic mechanism of bosentan regarding its anti-inflammatory effects. We and other investigators have demonstrated the strong contribution of inflammation to atherosclerosis vulnerability [8,39,40]. We also noticed a complementary pattern after bosentan and atorvastatin in the modulation of inflammatory mediators, focusing on TNF-a and MCP-1.…”

Itaconate suppresses atherosclerosis by activating a Nrf2-dependent antiinflammatory response in macrophages in mice

“…We examined the expression of select MMPs and TIMPs, and found that MMP9 and MMP12 were upregulated in atherosclerotic aortas from Acod1 –/– mice versus WT, at both mRNA and protein levels ( Supplemental Figure 3 , A and B). These MMPs have been found to promote plaque instability and increase atherosclerotic burden ( 22 , 23 ), consistent with more severe atherogenesis in Acod1 –/– versus WT mice.…”

PCSK9 inhibitor in acute ischemic stroke patient receiving mechanical thrombectomy: early outcomes and safety

“…Beyond the LDL cholesterol regulation, PCSK9 has been shown to have multiple roles in vascular diseases ( 7–10 ), PCSK9 inhibitors exhibit anti-inflammatory properties, contribute to the stabilization of atherosclerotic plaques ( 9 ), and reduce infarction volume, as seen in in-vitro and animal studies ( 11 , 12 ). These pleiotropic effects of PCSK9 inhibitors have also observed in small human studies ( 11 , 13 ), with follow-up studies using IVUS showing regression of atherosclerotic plaques ( 14 ). Based on these insights, several recent and ongoing studies have been employing PCSK9 inhibitors early in the treatment process and off-label for patients with acute myocardial infarction who are receiving percutaneous coronary intervention ( 15 , 16 ).…”