OBJECTIVE Galectin-3 (formerly known as Mac-2), encoded by the LGALS3 gene, is proposed to regulate macrophage adhesion, chemotaxis, and apoptosis. We investigated the role of galectin-3 in determining the inflammatory profile of macrophages and composition of atherosclerotic plaques. Approach and Results We observed increased accumulation of galectin-3-negative macrophages within advanced human, rabbit, and mouse plaques compared with early lesions. Interestingly, statin treatment reduced galectin-3-negative macrophage accrual in advanced plaques within hypercholesterolemic (apolipoprotein E deficient) Apoe-/- mice. Accordingly, compared with Lgals3+/+Apoe-/- mice, Lgals3-/-Apoe-/- mice displayed altered plaque composition through increased macrophagesmooth muscle cell ratio, reduced collagen content, and increased necrotic core area, characteristics of advanced plaques in humans. Additionally, macrophages from Lgals3-/- mice exhibited increased invasive capacity in vitro and in vivo. Furthermore, loss of galectin-3 in vitro and in vivo was associated with increased expression of proinflammatory genes including MMP (matrix metalloproteinase)-12, CCL2 (chemokine [C-C motif] ligand 2), PTGS2 (prostaglandin-endoperoxide synthase 2), and IL (interleukin)-6, alongside reduced TGF (transforming growth factor)-β1 expression and consequent SMAD signaling. Moreover, we found that MMP12 cleaves macrophage cell-surface galectin-3 resulting in the appearance of a 22-kDa fragment, whereas plasma levels of galectin-3 were reduced in Mmp12-/-Apoe-/- mice, highlighting a novel mechanism where MMP12-dependent cleavage of galectin-3 promotes proinflammatory macrophage polarization. Moreover, galectin-3-positive macrophages were more abundant within plaques of Mmp12-/-Apoe-/- mice compared with Mmp12+/+Apoe-/- animals. CONCLUSIONS This study reveals a prominent protective role for galectin-3 in regulating macrophage polarization and invasive capacity and, therefore, delaying plaque progression.Prostanoids are a group of bioactive lipids that are synthesized de novo from membrane phospholipid-released arachidonic acid and have diverse functions in normal physiology and disease. NSAIDs, which are among the most commonly used medications, ameliorate pain, fever, and inflammation by inhibiting COX (cyclooxygenase), which is the rate-limiting enzyme in the biosynthetic cascade of prostanoids. The use of NSAIDs selective for COX-2 inhibition increases the risk of a thrombotic event (eg, myocardial infarction and stroke). All NSAIDs are associated with an increased risk of heart failure. Substantial variation in clinical responses to aspirin exists and is associated with cardiovascular risk. Limited clinical studies suggest the involvement of prostanoids in vascular restenosis in patients who received angioplasty intervention. mPGES (microsomal PG [prostaglandin] E2 synthase)-1, an alternative target downstream of COX, has the potential to be therapeutically targeted for inflammatory disease, with diminished thrombotic risk relative to selective COX-2 inhibitors. mPGES-1-derived PGE2 critically regulates microcirculation via its receptor EP (receptor for prostanoid E) 4. This review summarizes the actions and associated mechanisms for modulating the biosynthesis of prostanoids in thrombosis, vascular remodeling, and ischemic heart disease as well as their therapeutic relevance.OBJECTIVE Healed plaques, signs of previous plaque destabilization, are frequently found in the coronary arteries. Healed plaques can now be diagnosed in living patients. We investigated the prevalence, angiographic, and optical coherence tomography features of healed plaques in patients with stable angina pectoris. Approach and Results Patients with stable angina pectoris who had undergone optical coherence tomography imaging were included. Healed plaques were defined as plaques with one or more signal-rich layers of different optical density. Patients were divided into 2 groups based on layered or nonlayered phenotype at the culprit lesion. Among 163 patients, 87 (53.4%) had layered culprit plaque. Patients with layered culprit plaque had more multivessel disease (62.1% versus 44.7%, P=0.027) and more angiographically complex culprit lesions (64.4% versus 35.5%, P less then 0.001). Layered culprit plaques had higher prevalence of lipid plaque (83.9% versus 64.5%, P=0.004), macrophage infiltration (58.6% versus 35.5%, P=0.003), calcifications (78.2% versus 63.2%, P=0.035), and thrombus (28.7% versus 14.5%, P=0.029). Lipid index (P=0.001) and percent area stenosis (P=0.015) were greater in the layered group. The number of nonculprit plaques, evaluated using coronary angiograms, tended to be greater in patients with layered culprit plaque (4.2±2.5 versus 3.5±2.1, P=0.053). Nonculprit plaques in patients with layered culprit lesion had higher prevalence of layered pattern (P=0.002) and lipid phenotype (P=0.005).  https://www.selleckchem.com/products/sf2312.html  Lipid index (P=0.013) and percent area stenosis (P=0.002) were also greater in this group. CONCLUSIONS In patients with stable angina pectoris, healed culprit plaques are common and have more features of vulnerability and advanced atherosclerosis both at culprit and nonculprit lesions.BACKGROUND Vascular injury and inflammation during percutaneous coronary intervention (PCI) are associated with increased risk of post-PCI adverse outcomes. Colchicine decreases neutrophil recruitment to sites of vascular injury. The anti-inflammatory effects of acute colchicine administration before PCI on subsequent myocardial injury are unknown. METHODS In a prospective, single-site trial, subjects referred for possible PCI (n=714) were randomized to acute preprocedural oral administration of colchicine 1.8 mg or placebo. RESULTS Among the 400 subjects who underwent PCI, the primary outcome of PCI-related myocardial injury did not differ between colchicine (n=206) and placebo (n=194) groups (57.3% versus 64.2%, P=0.19). The composite outcome of death, nonfatal myocardial infarction, and target vessel revascularization at 30 days (11.7% versus 12.9%, P=0.82), and the outcome of PCI-related myocardial infarction defined by the Society for Cardiovascular Angiography and Interventions (2.9% versus 4.7%, P=0.49) did not differ between colchicine and placebo groups.