Objective-Heterogeneous smooth muscle cell (SMC) populations have been described in the arteries of several species.We have investigated whether SMC heterogeneity is present in the porcine coronary artery, which is widely used as a model of restenosis. Methods and Results-By using 2 isolation methods, distinct medial populations were identified: spindle-shaped SMCs (S-SMCs) after enzymatic digestion, with a "hill-and-valley" growth pattern, and rhomboid SMCs (R-SMCs) after explantation, which grow as a monolayer. Moreover, the intimal thickening that was induced after stent implantation yielded a large proportion of R-SMCs. R-SMCs exhibited high proliferative and migratory activities and high urokinase activity and were poorly differentiated compared with S-SMCs. Heparin and transforming growth factor-2 inhibited proliferation and increased differentiation in both populations, whereas fibroblast growth factor-2 and platelet-derived growth factor-BB had the opposite effect. In addition, S-SMCs treated with fibroblast growth factor-2 or platelet-derived growth factor-BB or placed in coculture with coronary artery endothelial cells acquired a rhomboid phenotype. This change was reversible and was also observed with S-SMC clones, suggesting that it depends on phenotypic modulation rather than on selection. Conclusions-Our results show that 2 distinct SMC subpopulations can be recovered from the pig coronary artery media.The study of these subpopulations will be useful for understanding the mechanisms of restenosis. Key Words: intimal thickening Ⅲ restenosis Ⅲ endothelial cells Ⅲ myosin Ⅲ smoothelin S mooth muscle cell (SMC) replication and migration from the media into the intima are essential processes during the development and evolution of atheromatous plaque and restenosis. 1 There is now substantial experimental evidence to support the assumption that SMCs from the arterial wall of several species are phenotypically heterogeneous and that certain subsets of medial SMCs are particularly prone to accumulate within the intima under appropriate stimuli. [1][2][3] Two distinct SMC populations have been identified in the rat arterial media: spindle-shaped SMCs (S-SMCs) and epithelioid SMCs, with both exhibiting distinct biological features. 4 Epithelioid SMCs are capable of replicating in the absence of serum 4,5 and exhibit high migratory activity 5 that is correlated with increased tissue plasminogen activator (tPA) expression. 6 Epithelioid SMCs have been shown to be the predominant component of intimal thickening (IT). 7 Spindle-shaped and epithelioid clones can be recovered from adult rat normal media (NM) and IT, albeit in different proportions according to the origin. 5,8 These clones, irrespective of their origin, exhibit phenotypic features similar to those of the corresponding whole-cell populations, thus providing evidence that the NM contains cells capable of displaying each of the 2 phenotypes in vitro.To extend the notion of SMC heterogeneity to other species and to a well-accepted model for human athe...
AimsCoronary computed tomography angiography (CTA) has emerged as a non-invasive diagnostic method for patients with suspected coronary artery disease, but its usefulness in patients with complex coronary artery disease remains to be investigated. The present study sought to determine the agreement between separate heart teams on treatment decision-making based on either coronary CTA or conventional angiography. Methods and resultsSeparate heart teams composed of an interventional cardiologist, a cardiac surgeon, and a radiologist were randomized to assess the coronary artery disease with either coronary CTA or conventional angiography in patients with de novo left main or three-vessel coronary artery disease. Each heart team, blinded for the other imaging modality, quantified the anatomical complexity using the SYNTAX score and integrated clinical information using the SYNTAX Score II to provide a treatment recommendations based on mortality prediction at 4 years: coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or equipoise between CABG and PCI. The primary endpoint was the agreement between heart teams on the revascularization strategy. The secondary endpoint was the impact of fractional flow reserve derived from coronary CTA (FFRCT) on treatment decision and procedural planning. Overall, 223 patients were included. A treatment recommendation of CABG was made in 28% of the cases with coronary CTA and in 26% with conventional angiography. The agreement concerning treatment decision between coronary CTA and conventional angiography was high (Cohen’s kappa 0.82, 95% confidence interval 0.74–0.91). The heart teams agreed on the coronary segments to be revascularized in 80% of the cases. FFRCT was available for 869/1108 lesions (196/223 patients). Fractional flow reserve derived from coronary CTA changed the treatment decision in 7% of the patients.ConclusionIn patients with left main or three-vessel coronary artery disease, a heart team treatment decision-making based on coronary CTA showed high agreement with the decision derived from conventional coronary angiography suggesting the potential feasibility of a treatment decision-making and planning based solely on this non-invasive imaging modality and clinical information.Trial registration numberNCT02813473.
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