Vascular smooth muscle cells (VSMCs) are central players in carotid atherosclerosis plaque development. Although the precise mechanisms involved in plaque destabilization are not completely understood, it is known that VSMC proliferation and migration participate in plaque stabilization. In this study, we analyzed expression patterns of genes involved in carotid atherosclerosis development (e.g., transcription factors of regulation of SMC genes) of VSMCs located inside or outside the plaque lesion that may give clues about changes in phenotypic plasticity during atherosclerosis. VSMCs were isolated from 39 carotid plaques extracted from symptomatic and asymptomatic patients by endarterectomy. Specific biomarker expression, related with VSMC phenotype, was analyzed by qPCR, western immunoblot, and confocal microscopy. MYH11, CNN1, SRF, MKL2, and CALD1 were significantly underexpressed in VSMCs from plaques compared with VSMCs from a macroscopically intact (MIT) region, while SPP1, KLF4, MAPLC3B, CD68, and LGALS3 were found significantly upregulated in plaque VSMCs versus MIT VSMCs. The gene expression pattern of arterial VSMCs from a healthy donor treated with 7-ketocholesterol showed high similarity with the expression pattern of carotid plaque VSMCs. Our results indicate that VSMCs isolated from plaque show a typical SMC dedifferentiated phenotype with macrophage-like features compared with VSMCs isolated from a MIT region of the carotid artery. Additionally, MYH11, KLF5, and SPP1 expression patterns were found to be associated with symptomatology of human carotid atherosclerosis.

Carotid artery atherosclerosis is a risk factor to develop cerebrovascular disease. Atheroma plaque can become instable and provoke a cerebrovascular event or else remain stable as asymptomatic type. The exact mechanism involved in plaque destabilization is not known but includes among other events smooth muscle cell (SMC) differentiation. The goal of this study was to perform thorough analysis of gene expression differences in SMCs isolated from carotid symptomatic versus asymptomatic plaques. Comparative transcriptomics analysis of SMCs based on RNAseq technology identified 67 significant differentially expressed genes and 143 significant differentially expressed isoforms in symptomatic SMCs compared with asymptomatic. 37 of top-scoring genes were further validated by digital PCR. Enrichment and network analysis shows that the gene expression pattern of SMCs from stable asymptomatic plaques is suggestive for an osteogenic phenotype, while that of SMCs from unstable symptomatic plaque correlates with a senescence-like phenotype. Osteogenic-like phenotype SMCs may positively affect carotid atheroma plaque through participation in plaque stabilization via bone formation processes. On the other hand, plaques containing senescence-like phenotype SMCs may be more prone to rupture. Our results substantiate an important role of SMCs in carotid atheroma plaque disruption.

BackgroundBecause of the unique electromagnetic characteristics of the magnetoelastic microwire, the changes in the pressure of a fluid will provoke a variation of the mechanical pressure on the sensor, which will cause a variation of its magnetization that will be detectable wirelessly. Thus, a wireless system can be developed for following up vascular surgery procedures.Methods and ResultsThe sensor consists of a magnetoelastic microwire ring, which was integrated into an in vitro model with pulsatile flow. Different degrees of stenosis were simulated in different locations both in bovine artery as well as in a polytetrafluoroethylene anastomosis. A Fourier analysis of the registered signals and a statistical analysis using Pearson test and receiver operating characteristic (ROC) curves were made. A Pearson index of 0.945 (P<0.001) was obtained between the invasive pressure of the fluid and the power of the signal transmitted by the sensor in bovine artery. The sensor obtained very good ROC curves upon analyzing the signals registered, both in the case of preanastomotic stenosis (area under the curve [AUC], 0.98; 95% CI, 0.97–1.00), of anastomosis (AUC, 0.93; 95% CI, 0.86–0.99), as well as distal (AUC, 0.88; 95% CI, 0.79–0.98), compared to the control group.ConclusionsThe magnetoelastic microwire has shown that it is capable of detecting, locating, and quantifying the degree of stenosis in bovine artery, as well as in a latero‐terminal anastomosis, with a high statistical potency. For the first time, a wireless in vitro sensor has been developed for the postoperative follow‐up of vascular surgery procedures.

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