Short-Term and Long-Term Fluvastatin Inhibit Effects of Thrombospondin-1 on Human Vascular Smooth Muscle Cells.

Introduction: Vascular smooth muscle cells are important in intimal hyperplasia. Thrombospondin-1 is a matricellular protein involved in the vascular injury response. Statins are cholesterol lowering drugs that have beneficial cardiovascular effects.

Biomarkers and molecular endotypes of sarcoidosis: lessons from omics and non-omics studies.

Sarcoidosis is a chronic granulomatous disorder characterized by unknown etiology, undetermined mechanisms, and non-specific therapies except TNF blockade. To improve our understanding of the pathogenicity and to predict the outcomes of the disease, the identification of new biomarkers and molecular endotypes is sorely needed. In this study, we systematically evaluate the biomarkers identified through Omics and non-Omics approaches in sarcoidosis.

"Modern Endovascular Therapy".

Introduction: The past 25 years have been witness to a revolution in how vascular care is delivered. The majority of arterial and venous interventions have converted from open surgery to minimally invasive percutaneous endovascular procedures.

Methods: This surgical innovations symposium article reviews current endovascular therapy in multiple vascular beds with a primary focus on carotid artery occlusive disease, aortic pathologies, and lower extremity arterial occlusive disease.

Thrombospondin-5 and fluvastatin promote angiogenesis and are protective against endothelial cell apoptosis.

The thrombospondins (TSPs), multifunctional matricellular proteins, are known mediators of endothelial cell (EC) angiogenesis and apoptosis. TSP-1, an antiangiogenic molecule, is important in the progression of vascular disease, in part by inducing EC apoptosis. TSP-2, although less studied, also induces EC apoptosis and inhibits angiogenesis.

Inhibition of heat shock protein 90 attenuates post‑angioplasty intimal hyperplasia.

Intimal hyperplasia (IH) is a pathologic process that leads to restenosis after treatment for peripheral arterial disease. Heat shock protein 90 (HSP90) is a molecular chaperone that regulates protein maturation. Activation of HSP90 results in increased cell migration and proliferation.

The role of the Vascular Surgery Board in surgical education.

The American Board of Surgery (ABS) has more than 80 years of both direct and indirect involvement in US surgical education, with its primary role being certification of graduates of Accreditation Council for Graduate Medical Education-approved surgical training programs. The ABS's impact on education has been at multiple levels, including the development of the content and administration of qualifying and certifying examinations; original education research based on the Board's unique data sets; and surgical training and education-related initiatives in partnership with multiple regulatory bodies and surgical societies. Within these efforts, by incremental steps, the specialty of vascular surgery attained recognition as a primary specialty of the ABS, and the Vascular Surgery Board of the ABS was established 20 years ago, in 1998.

Frailty and Biomarkers of Frailty Predict Outcome in Veterans After Open and Endovascular Revascularization.

Background: Frailty predicts poor outcome after vascular surgery. We determined the predictive utility of the modified frailty index (mFI) after first-time revascularization and identified biomarkers of frailty predictive of outcome in veterans with peripheral arterial disease.

Methods: A retrospective study was performed of first-time revascularizations (open surgery [OS] and endovascular surgery [ES]) in male veterans (2003-2016).

Intraluminal Delivery of Simvastatin Attenuates Intimal Hyperplasia After Arterial Injury.

Introduction: Oral statins reduce intimal hyperplasia (IH) after arterial injury by only ∼25%. Alternative drug delivery systems have gained attention as carriers for hydrophobic drugs. We studied the effects of simvastatin (free vs hyaluronic acid-tagged polysialic acid-polycaprolactone micelles) on vascular smooth muscle cell (VSMC) migration, VSMC proliferation and intimal hyperplasia.

Fluvastatin inhibits intimal hyperplasia in wild-type but not Thbs1-null mice.

Background: Thrombospondin-1 (TSP-1) is functionally important to intimal hyperplasia (IH) development. Statin drugs have beneficial pleiotropic effects, including reduced IH; however, the effect of statins on IH in a TSP-1-independent setting is unknown.

Hypothesis: Statins will be less effective in attenuating IH after vascular injury in TSP-1-null (Thbs1) mice compared with wild-type (WT) mice.

Postoperative conversion disorder.

Conversion disorder is a psychiatric disorder in which psychological stress causes neurologic deficits. A 28-year-old female surgical patient had uneventful general anesthesia and emergence but developed conversion disorder 1 hour postoperatively. She reported difficulty speaking, right-hand numbness and weakness, and right-leg paralysis.

Dyslipidemia Part 2: Review of Dyslipidemia Treatment in Patients With Noncoronary Vascular Disease.

Dyslipidemia is one of the major modifiable risk factors associated with atherosclerotic cardiovascular disease. Appropriate modification of lipid profiles reduces the progression of atherosclerosis in vessel walls across all vascular beds. The management of dyslipidemia has evolved over the last several decades, especially since the discovery of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, also known as statins.

Dyslipidemia Part 1--Review of Lipid Metabolism and Vascular Cell Physiology.

Dyslipidemia, more specifically, high-serum low-density lipoproteins and low-serum high-density lipoproteins, are known risk factors for cardiovascular disease. The current clinical treatment of dyslipidemia represents the outcome of a large body of fundamental basic science research on lipids, lipid metabolism, and the effects of different lipids on cellular components of the artery, inflammatory cells, and platelets. In general, lower density lipids activate intracellular pathways to increase local and systemic inflammation, monocyte adhesion, endothelial cell dysfunction and apoptosis, and smooth muscle cell proliferation, resulting in foam cell formation and genesis of atherosclerotic plaque.

Thrombospondin-1 differentially regulates microRNAs in vascular smooth muscle cells.

Thrombospondin-1 (TSP-1) is an important regulator of vascular smooth muscle cell (VSMC) physiology and gene expression. MicroRNAs (microRNA), small molecules that regulate protein translation, have emerged as potent regulators of cell function. MicroRNAs have been shown to be involved in intimal hyperplasia, atherosclerosis, and upregulated in the vasculature in diabetes.

Dyslipidemia regulates thrombospondin-1-induced vascular smooth muscle cell chemotaxis.

Unlabelled: Dyslipidemia is a risk factor for intimal hyperplasia (IH). Key to IH is vascular smooth muscle cell (VSMC) migration. Thrombospondin-1 (TSP-1) is a matricellular protein that stimulates VSMC migration.

Thrombospondin-1, -2 and -5 have differential effects on vascular smooth muscle cell physiology.

Introduction: The thrombospondins (TSPs) are matricellular proteins that exert multifunctional effects by binding cytokines, cell-surface receptors and other proteins. TSPs play important roles in vascular pathobiology and are all expressed in arterial lesions. The differential effects of TSP-1, -2, and -5 represent a gap in knowledge in vascular smooth muscle cell (VSMC) physiology.

Correlation of hemoglobin A1C level with surgical outcomes: Can tight perioperative glucose control reduce infection and cardiac events?

"Optimal" control of serum glucose levels is an important principle in the successful management of diabetes mellitus. Conversely, poorly controlled serum glucose levels are associated with negative sequelae, including accelerated progression of cardiovascular disease, increased mortality, and increased perioperative complications. The importance of glycemic control as a part of appropriate perioperative management is reviewed and target values are recommended.

Statins and nitric oxide donors affect thrombospondin 1-induced chemotaxis.

Background: Thrombospondin 1 (TSP-1) induces vascular smooth muscle cell (VSMC) migration and intimal hyperplasia. Statins and nitric oxide (NO) donors decrease intimal hyperplasia. We previously showed that statins (long-term exposure) and NO donors inhibit TSP-1-induced VSMC chemotaxis.

Thrombospondin-1-induced vascular smooth muscle cell migration and proliferation are functionally dependent on microRNA-21.

Objectives: Thrombospondin-1 (TSP-1) is a matricellular glycoprotein released from platelets at sites of arterial injury and is important in neointima development after balloon angioplasty. MicroRNAs are small noncoding RNAs that function by binding target gene mRNA and inhibiting protein translation. MicroRNA-21 (miR-21) is up-regulated after angioplasty, and inhibition of miR-21 leads to decreased intimal hyperplasia.

Thrombospondin-1-induced smooth muscle cell chemotaxis and proliferation are dependent on transforming growth factor-β2 and hyaluronic acid synthase.

Angioplasty causes local vascular injury, leading to the release of thrombospondin-1 (TSP-1), which stimulates vascular smooth muscle cell (VSMC) migration and proliferation, important steps in the development of intimal hyperplasia. Transforming growth factor beta 2 (TGF-β2) and hyaluronic acid synthase (HAS) are two pro-stenotic genes upregulated in VSMCs by TSP-1. We hypothesized that inhibition of TGF-β2 or HAS would inhibit TSP-1-induced VSMC migration, proliferation, and TSP-1 signaling.

Bilateral lower extremity acute thromboembolism as first presentation for cancer in a child: an interesting report.

Although it rarely occurs in children, acute arterial thromboembolism can cause significant morbidity and mortality. Rapid diagnosis and prompt treatment can increase the chances of survival with a functional limb. We describe the case of a 10-year-old boy with acute bilateral lower extremity ischemia due to arterial thromboemboli originating from a rare cancer.

The role of hyaluronic acid in atherosclerosis and intimal hyperplasia.

Atherosclerosis is a chronic inflammatory condition of the blood vessel wall that can lead to arterial narrowing and subsequent vascular compromise. Although there are a variety of open and endovascular procedures used to alleviate the obstructions caused by atherosclerotic plaque, blood vessel instrumentation itself can lead to renarrowing of the vessel lumen through intimal hyperplasia, wound contracture, or a combination of the two. While the cell types involved in both atherosclerosis and vessel renarrowing after surgical intervention are largely characterized, current research has shown that components of the extracellular matrix are also important in the pathogenesis of the aforementioned processes.

The effects of nicotine on vascular smooth muscle cell chemotaxis induced by thrombospondin-1 and fibronectin.

Background: Vascular smooth muscle cell (VSMC) migration is an important process in many vascular disorders. Nicotine, thrombospondin-1 (TSP-1) and fibronectin (Fn) separately induce VSMC migration. The hypothesis of this study was that nicotine treatment of vascular cells would augment TSP-1-induced and Fn-induced VSMC migration.

Vascular smooth muscle cell migration induced by domains of thrombospondin-1 is differentially regulated.

Background: Thrombospondin-1 (TSP-1) stimulates vascular smooth muscle cell (VSMC) migration via defined intracellular signaling pathways. The aim of this study was to examine the signaling pathways whereby TSP-1 folded domains (amino-terminal [NH(2)], procollagen homology [PCH], all 3 type 1 repeats [3TSR], and a single recombinant protein containing the 3rd type 2 repeat, the type 3 repeats, and the carboxyl-terminal [E3T3C1]) induce VSMC migration.

Methods: Quiescent VSMCs were pretreated with serum-free media or inhibitors: PP2 (c-Src), LY294002 (phosphatidylinositol 3-kinase), FPT (Ras), Y27632 (Rho kinase), SB202190 (p38 kinase), and PD98059 (extracellular signal-regulated kinase).