Vascular smooth muscle contraction is suppressed by feedback dilation mediated by the endothelium. In skeletal muscle arterioles, this feedback can be activated by Ca signals passing from smooth muscle through gap junctions to endothelial cells, which protrude through holes in the internal elastic lamina to make contact with vascular smooth muscle cells. Although hypothetically either Ca or inositol trisphosphate (IP) may provide the intercellular signal, it is generally thought that IP diffusion is responsible. We provide evidence that Ca entry through L-type voltage-dependent Ca channels (VDCCs) in vascular smooth muscle can pass to the endothelium through positions aligned with holes in the internal elastic lamina in amounts sufficient to activate endothelial cell Ca signaling. In endothelial cells in which IP receptors (IPRs) were blocked, VDCC-driven Ca events were transient and localized to the endothelium that protrudes through the internal elastic lamina to contact vascular smooth muscle cells. In endothelial cells in which IPRs were not blocked, VDCC-driven Ca events in endothelial cells were amplified to form propagating waves. These waves activated voltage-insensitive, intermediate-conductance, Ca-activated K (IK) channels, thereby providing feedback that effectively suppressed vasoconstriction and enabled cycles of constriction and dilation called vasomotion. Thus, agonists that stimulate vascular smooth muscle depolarization provide Ca to endothelial cells to activate a feedback circuit that protects tissue blood flow.

Body mechanics in the nematode Caenorhabditis elegans are central to both mechanosensation and locomotion. Previous work revealed that the mechanics of the outer shell, rather than internal hydrostatic pressure, dominates stiffness. This shell is comprised of the cuticle and the body wall muscles, either of which could contribute to the body mechanics. Here, we tested the hypothesis that the muscles are an important contributor by modulating muscle tone using optogenetic and pharmacological tools, and measuring animal stiffness using piezoresistive microcantilevers. As a proxy for muscle tone, we measured changes in animal length under the same treatments. We found that treatments that induce muscle contraction generally resulted in body shortening and stiffening. Conversely, methods to relax the muscles more modestly increased length and decreased stiffness. The results support the idea that body wall muscle activation contributes significantly to and can modulate C. elegans body mechanics. Modulation of body stiffness would enable nematodes to tune locomotion or swimming gaits and may have implications in touch sensation.

Significant racial disparities exist in outcomes after lower extremity procedures in patients with PAD, with regional variation contributing to perioperative but not long-term outcome disparities. Underperforming regions should use these data to generate quality improvement projects, as understanding the etiology of these disparities is critical to improving the care of all patients with PAD.

Aims Coronary microvascular smooth muscle cells (SMCs) respond to luminal pressure by developing myogenic tone (MT), a process integral to the regulation of microvascular perfusion. The cellular mechanisms underlying poor myogenic reactivity in patients with heart valve disease are unknown and form the focus of this study. Methods and Results Intramyocardial coronary micro-arteries (IMCAs) isolated from human and pig right atrial appendage (RA) and left ventricular (LV) biopsies were studied using pressure myography combined with confocal microscopy. All RA- and LV-IMCAs from organ donors and pigs developed circa 25% MT. In contrast, 44% of human RA-IMCAs from 88 patients with heart valve disease had poor (<10%) MT yet retained cell viability and an ability to raise cytoplasmic Ca2+ in response to vasoconstrictor agents. Comparing across human heart chambers and species we found that based on patient medical history and six tests, the strongest predictor of poor MT in IMCAs was increased expression of the synthetic marker caldesmon relative to the contractile marker SM-myosin heavy chain. In addition, high resolution imaging revealed a distinct layer of longitudinally-aligned SMCs between ECs and radial SMCs, and we show poor MT was associated with disruptions in these cellular alignments. Conclusions These data demonstrate the first use of atrial and ventricular biopsies from patients and pigs to reveal that impaired coronary MT reflects a switch of viable SMCs towards a synthetic phenotype, rather than a loss of SMC viability. These arteries represent a model for further studies of coronary microvascular contractile dysfunction.

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The artery wall is equipped with a water permeation barrier that allows blood to flow at high pressure without significant water leak. The precise location of this barrier is unknown despite its importance in vascular function and its contribution to many vascular complications when it is compromised. Herein we map the water permeability in intact arteries, using coherent anti-Stokes Raman scattering (CARS) microscopy and isotopic perfusion experiments. Generation of the CARS signal is optimized for water imaging with broadband excitation. We identify the water permeation barrier as the endothelial basolateral membrane and show that the apical membrane is highly permeable. This is confirmed by the distribution of the AQP1 water channel within endothelial membranes. These results indicate that arterial pressure equilibrates within the endothelium and is transmitted to the supporting basement membrane and internal elastic lamina macromolecules with minimal deformation of the sensitive endothelial cell. Disruption of this pressure transmission could contribute to endothelial cell dysfunction in various pathologies.

Within a matter of 48 hours, the promotion of the article entitled "Prevalence of unprofessional social media content among young vascular surgeons," aptly demonstrated the power of social media and the dangers of unconscious bias as it spread across Twitter with the #MedBikini tag. In response, vascular surgeons from around the world have come together in a call to action to address the article and highlight the misogynistic, racist, and oppressive issues facing young surgeons today. We, as female vascular surgery trainees, would like to make our own call to action. The publication of this article (now appropriately retracted) has encouraged important dialogue among female vascular surgeons, male colleagues who support #HeforShe initiatives, other disadvantaged and marginalized groups in surgery, and the future generation of surgeons who will pave the path forward. We have converged to discuss the current climate of our specialty and have determined that now is an opportunity for change.It is essential that we pursue ethics, as well as excellence, in surgical practice and research. The inherent conscious and unconscious biases, poor study design, and unethical data collection methods within the article have demonstrated a critical flaw within the editorial process of the Journal of Vascular Surgery (JVS). We are disappointed to find ourselves represented by the article. The publication was both tone deaf toward, and discriminatory against, us as professionals, trainees, and women. As vascular surgeons, we must hold ourselves to a higher standard. Our call to action for the JVS includes the following:1. Re-examine the review process for publication of ethical abstracts from regional and national meetings and manuscripts, and provide training in ethical research for all editors and reviewers.

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