Abstract-Atherosclerosis, formerly considered a bland lipid storage disease, actually involves an ongoing inflammatory response. Recent advances in basic science have established a fundamental role for inflammation in mediating all stages of this disease from initiation through progression and, ultimately, the thrombotic complications of atherosclerosis. These new findings provide important links between risk factors and the mechanisms of atherogenesis. Clinical studies have shown that this emerging biology of inflammation in atherosclerosis applies directly to human patients. Elevation in markers of inflammation predicts outcomes of patients with acute coronary syndromes, independently of myocardial damage. In addition, low-grade chronic inflammation, as indicated by levels of the inflammatory marker C-reactive protein, prospectively defines risk of atherosclerotic complications, thus adding to prognostic information provided by traditional risk factors. Moreover, certain treatments that reduce coronary risk also limit inflammation. In the case of lipid lowering with statins, this anti-inflammatory effect does not appear to correlate with reduction in low-density lipoprotein levels. These new insights into inflammation in atherosclerosis not only increase our understanding of this disease, but also have practical clinical applications in risk stratification and targeting of therapy for this scourge of growing worldwide importance. Key Words: endothelium Ⅲ inflammation Ⅲ atherosclerosis Ⅲ proteins O ver the last dozen years, appreciation of the role of inflammation in atherosclerosis has burgeoned. Although it was formerly considered a bland lipid storage disease, substantial advances in basic and experimental science have illuminated the role of inflammation and the underlying cellular and molecular mechanisms that contribute to atherogenesis. Compelling evidence for the importance of inflammation and atherosclerosis at both the basic and clinical level has evolved in parallel. Accumulating data indicate that insights gained from the link between inflammation and atherosclerosis can yield predictive and prognostic information of considerable clinical utility. This review summarizes the experimental and clinical evidence for inflammation in atherosclerosis, and assesses the current state of knowledge regarding the triggers for inflammation in this disease. We will evaluate the participation of inflammation in the acute coronary syndromes (ACS) and review the data supporting the use of inflammatory markers as prognostic and predictive instruments in the context both of ACS and of prediction of risk for various complications of atherosclerosis. Finally, we will consider how new insights into inflammation in atherosclerosis may identify innovative therapeutic strategies to improve outcomes of individuals at risk for or affected by this scourge of growing worldwide importance. The Scientific Basis of Inflammation in AtherogenesisIn a variety of animal models of atherosclerosis, signs of inflammation occur hand-in-ha...

Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846 .).

Serum concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with serum lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 × 10-8), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (e.g., CYP7A1, NPC1L1, and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and impact lipid traits in three non-European populations (East Asians, South Asians, and African Americans). Our results identify several novel loci associated with serum lipids that are also associated with CAD. Finally, we validated three of the novel genes—GALNT2, PPP1R3B, and TTC39B—with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.