A fully automated, field-based, wireless network that transmits ECGs automatically to offsite cardiologists for the early evaluation and triage of patients with STEMI shortens D2B times, reduces infarct size, limits ejection fraction reduction, and shortens LOS.

Vascular smooth muscle cells (VSMCs) are the predominant cell type in the arterial wall and normally adopt a quiescent, contractile phenotype to regulate vascular tone. In the arterial wall, VSMCs are exposed to multiple mechanical cues, including stretch and matrix stiffness, which regulate VSMC contraction. However, during ageing and in vascular disease, such as atherosclerosis, hypertension and vascular calcification, the arterial wall stiffens and VSMC contraction contributes to this process. VSMCs display remarkable plasticity and changes in their mechanical environment promote VSMCs to adopt a proliferative, synthetic phenotype. VSMC phenotypic modulation is associated with altered expression of contractile proteins that generate actomyosin-based force. However, our understanding of precise mechanisms whereby altered mechanical landscape and mechanotransduction influence VSMC contraction remains limited. In this review, we discuss the present literature describing how VSMCs sense and respond to changes in their mechanical environment and how these changes influence VSMC contraction.

Vascular smooth muscle cells (VSMCs) are the predominant cell type in the blood vessel wall. Changes in VSMC actomyosin activity and morphology are prevalent in cardiovascular disease. The actin cytoskeleton actively defines cellular shape and the LInker of Nucleoskeleton and Cytoskeleton (LINC) complex, comprised of nesprin and the Sad1p, UNC-84 (SUN)-domain family members SUN1/2, has emerged as a key regulator of actin cytoskeletal organisation. Although SUN1 and SUN2 function is partially redundant, they possess specific functions and LINC complex composition is tailored for cell-type-specific functions. We investigated the importance of SUN1 and SUN2 in regulating actomyosin activity and cell morphology in VSMCs. We demonstrate that siRNA-mediated depletion of either SUN1 or SUN2 altered VSMC spreading and impaired actomyosin activity and RhoA activity. Importantly, these findings were recapitulated using aortic VSMCs isolated from wild-type and SUN2 knockout (SUN2 KO) mice. Inhibition of actomyosin activity, using the rho-associated, coiled-coil-containing protein kinase1/2 (ROCK1/2) inhibitor Y27632 or blebbistatin, reduced SUN2 mobility in the nuclear envelope and decreased the association between SUN2 and lamin A, confirming that SUN2 dynamics and interactions are influenced by actomyosin activity. We propose that the LINC complex exists in a mechanical feedback circuit with RhoA to regulate VSMC actomyosin activity and morphology.

Vascular smooth muscle cells (VSMCs) are the predominant cell type in the medial layer of the aortic wall and normally exist in a quiescent, contractile phenotype where actomyosin-derived contractile forces maintain vascular tone. However, VSMCs are not terminally differentiated and can dedifferentiate into a proliferative, synthetic phenotype. Actomyosin force generation is essential for the function of both phenotypes. Whilst much is already known about the mechanisms of VSMC actomyosin force generation, existing assays are either low throughput and time consuming, or qualitative and inconsistent. In this study, we use polyacrylamide hydrogels, tuned to mimic the physiological stiffness of the aortic wall, in a VSMC contractility assay. Isolated VSMC area decreases following stimulation with the contractile agonists angiotensin II or carbachol. Importantly, the angiotensin II induced reduction in cell area correlated with increased traction stress generation. Inhibition of actomyosin activity using blebbistatin or Y-27632 prevented angiotensin II mediated changes in VSMC morphology, suggesting that changes in VSMC morphology and actomyosin activity are core components of the contractile response. Furthermore, we show that microtubule stability is an essential regulator of isolated VSMC contractility. Treatment with either colchicine or paclitaxel uncoupled the morphological and/or traction stress responses of angiotensin II stimulated VSMCs. Our findings support the tensegrity model of cellular mechanics and we demonstrate that microtubules act to balance actomyosin-derived traction stress generation and regulate the morphological responses of VSMCs.

Round-the-clock, in-hospital interventional cardiology team consistently and significantly reduces D2B time, in-hospital cardiovascular mortality, MACE, and 1-year mortality in patients with STEMI.

Vascular smooth muscle cells (VSMCs) are the predominant cell type in the blood vessel wall and normally adopt a quiescent, contractile phenotype. VSMC migration is tightly controlled, however, disease associated changes in the soluble and insoluble environment promote VSMC migration. Classically, studies investigating VSMC migration have described the influence of soluble factors. Emerging data has highlighted the importance of insoluble factors, including extracellular matrix stiffness and porosity. In this review, we will recap on the important signalling pathways that regulate VSMC migration and reflect on the potential importance of emerging regulators of VSMC function.

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The rate of left ventricular (LV) pressure fall (dP/dtmin) is reportedly altered by contractility and LV stress. To explore the possibility that the ratio of dP/dtmin to dicrotic notch pressure (DTES) measures contractility, 243 subjects including 23 normals (group I) were studied. In 35 patients of group II (16 with mitral stenosis, 7 with atrial septal defect, and 12 with cor pulmonale) DTES, as an index of contractility (Cy Ix) measuring force-velocity-length relationship, was insignificantly different from group I (DTES and Cy Ix in group I = 21.6 ± 0.6 s-1 and 1.34 ± 0.04 muscle lengths/s/cm and 18.8 ± 1.8 s-1 and 1.55 ± 0.24 muscle lengths/s/cm in group II, respectively). With significantly reduced Cylx (1.05 ± 0.04, p < 0.01), DTES was likewise reduced (19.0 ± 0.5, p < 0.01) in 163 patients with compensated LV disease (47 with alcoholic cardiomyopathy, 24 coronary artery disease, 48 valve disease, 10 hypertensives and 34 with other heart muscle diseases). Like the Cy Ix (0.70 ± 0.05, p < 0.001), DTES was even lower (13.3 ± 0.6, p < 0.001) in 15 patients with decompensated LV (group IV). Like Cy Ix, this ratio changed significantly with acute changes in inotropy (exercise and pacing), but not with preload (dextran infusion). Basal heart rate, preload and afterload did not influence DTES. Furthermore, DTES correlated significantly in all groups and subgroups with two indices of contractility, VCE(velocity of contractile element) at peak isometric stress, and Cy Ix (r = 0.68 and 0.70, respectively, each p < 0.001) measured in this study. These results indicate that DTES provides a simple, reliable, and useful measure of the contractile state of LV myocardium in man, independent of preload and afterload.