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l responsibilities, and being in the position of a "semi-physician." These findings shed light on the identity transition from student to practitioner within such a curricular structure.In the 1980s and early 1990s, Dr. Barrie Carter served as the Chief of the Laboratory of Molecular and Cellular Biology, in the National Institute of Diabetes and Digestive and Kidney Diseases, at the National Institutes of Health. During that time, his group performed seminal work in Adeno-Associated Virus Type 2 (AAV2) biology, including creating one of the first infectious clones of AAV2 and some of the first packaged AAV2 vectors. This work contributed substantially to the development of AAVs as gene therapy vectors. Part of the success of the group was due to Dr. Carter's ability to attract and manage a diverse team of talented individuals who synergized into a collaborative group that was more than the sum of its parts. This review describes some of the promising practices employed by the Carter group, which allowed such a diverse group to function so well. These practices included promoting a culture of co-mentoring, open communication, and respectful questioning.Arterial stiffness is a major independent risk factor for cardiovascular complications causing isolated systolic hypertension and increased pulse pressure in the microvasculature of target organs. Stiffening of the arterial wall is determined by common mechanisms including reduced elastin/collagen ratio, production of elastin cross-linking, reactive oxygen species-induced inflammation, calcification, vascular smooth muscle cell stiffness, and endothelial dysfunction. This brief review will discuss current biological mechanisms by which other cardiovascular risk factors (eg. aging, hypertension, diabetes mellitus, and chronic kidney disease) cause arterial stiffness, with a particular focus on recent advances regarding nuclear mechanotransduction, mitochondrial oxidative stress, metabolism and dyslipidemia, genome mutations, and epigenetics. Targeting these different molecular pathways at different time of cardiovascular risk factor exposure may be a novel approach for discovering drugs to reduce arterial stiffening without affecting artery strength and normal remodeling.It is estimated that >2 million patients are living with an amputation in the United States. Peripheral artery disease (PAD) and diabetes mellitus account for the majority of nontraumatic amputations. The standard measurement to diagnose PAD is the ankle-brachial index, which integrates all occlusive disease in the limb to create a summary value of limb artery occlusive disease. Despite its accuracy, ankle-brachial index fails to well predict limb outcomes. There is an emerging body of literature that implicates microvascular disease (MVD; ie, retinopathy, nephropathy, neuropathy) as a systemic phenomenon where diagnosis of MVD in one capillary bed implicates microvascular dysfunction systemically. MVD independently associates with lower limb outcomes, regardless of diabetic or PAD status. The presence of PAD and concomitant MVD phenotype reveal a synergistic, rather than simply additive, effect. Darovasertib The higher risk of amputation in patients with MVD, PAD, and concomitant MVD and PAD should prompt aggressive foot surveillance and diagnosis of both conditions to maintain ambulation and prevent amputation in older patients.OBJECTIVE Vascular progenitor cells (VPCs), which are able to differentiate into both endothelial cells and smooth muscle cells, have the potential for treatment of ischemic diseases. Generated by pluripotent stem cells, VPCs carry the risk of tumorigenicity in clinical application. This issue could be resolved by direct lineage conversion, the induction of functional cells from another lineage by using only lineage-restricted transcription factors. Here, we show that induced VPCs (iVPCs) can be generated from fibroblasts by ETS (E-twenty six) transcription factors, Etv2 and Fli1. Approach and Results Mouse fibroblasts were infected with lentivirus encoding Etv2 and Fli1. Cell colonies appeared in Fli1- and Etv2/Fli1-infected groups and were mechanically picked. The identity of cell colonies was confirmed by proliferation assay and reverse-transcription polymerase chain reaction with vascular markers. Etv2/Fli1- infected cell colonies were sorted by CD144 (CDH5, VE-cadherin). We defined that CD144-positive iVPCs maintained its own population and expanded stably at multiple passages. iVPCs could differentiate into functional endothelial cells and smooth muscle cells by a defined medium. The functionalities of iVPC-derived endothelial cells and smooth muscle cells were confirmed by analyzing LDL (low-density lipoprotein) uptake, carbachol-induced contraction, and tube formation in vitro. Transplantation of iVPCs into the ischemic hindlimb model enhanced blood flow without tumor formation in vivo. Human iVPCs were generated by ETV2 and FLI1. CONCLUSIONS We demonstrate that ischemic disease curable iVPCs, which have self-renewal and bipotency, can be generated from mouse fibroblasts by enforced ETS family transcription factors, Etv2 and Fli1 expression. Our simple strategy opens insights into stem cell-based ischemic disease therapy.OBJECTIVE HuR (human antigen R)-an RNA-binding protein-is involved in regulating mRNA stability by binding adenylate-uridylate-rich elements. This study explores the role of HuR in the regulation of smooth muscle contraction and blood pressure. Approach and Results Vascular HuRSMKO (smooth muscle-specific HuR knockout) mice were generated by crossbreeding HuRflox/flox mice with α-SMA (α-smooth muscle actin)-Cre mice. As compared with CTR (control) mice, HuRSMKO mice showed hypertension and cardiac hypertrophy. HuR levels were decreased in aortas from hypertensive patients and SHRs (spontaneously hypertensive rats), and overexpression of HuR could lower the blood pressure of SHRs. Contractile response to vasoconstrictors was increased in mesenteric artery segments isolated from HuRSMKO mice. The functional abnormalities in HuRSMKO mice were attributed to decreased mRNA and protein levels of RGS (regulator of G-protein signaling) protein(s) RGS2, RGS4, and RGS5, which resulted in increased intracellular calcium increase.