J Am Coll Cardiol. 2018 May 15;71(19):2092-2102. doi: 10.1016/j.jacc.2018.02.073.
Local Low Shear Stress and Endothelial Dysfunction in Patients With Nonobstructive Coronary Atherosclerosis.
Siasos G1, Sara JD2, Zaromytidou M1, Park KH2, Coskun AU1, Lerman LO2, Oikonomou E3, Maynard CC4, Fotiadis D5, Stefanou K5, Papafaklis M5, Michalis L5, Feldman C1, Lerman A2, Stone PH6.
Author information 1Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts.2Division of Cardiovascular Disease, Mayo Clinic, Rochester, Minnesota.31(st) Department of Cardiology, National and Kapodistrian University of Athens Medical School, Hippokration Hospital, Athens, Greece.4University of Washington, Seattle, Washington.5Medical School, University of Ioannina, Ioannina, Greece.6Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: firstname.lastname@example.org.
Abstract BACKGROUND: Local hemodynamic factors are important determinants of atherosclerotic plaque development and progression. OBJECTIVES: The goal of this study was to determine the association between low endothelial shear stress (ESS) and microvascular and epicardial endothelial dysfunction in patients with early atherosclerosis. METHODS: Sixty-five patients (mean age 52 ± 11 years) with nonobstructive coronary atherosclerosis (luminal diameter stenosis <30%) were included. Microvascular and epicardial coronary endothelial function was assessed by using intracoronary acetylcholine infusion. Vascular profiling, using 2-plane coronary angiography and intravascular ultrasound, was used to reconstruct the three-dimensional anatomy of the left anterior descending artery. Each reconstructed artery was divided into sequential 3-mm segments and analyzed for local ESS with computational fluid dynamics; that is, lower ESS levels at both a 3-mm regional level (average ESS and low ESS) and at a vessel level (lowest ESS per artery) and for plaque characteristics (plaque area, plaque thickness, and plaque burden). RESULTS: Coronary segments in arteries with abnormal microvascular function exhibited lower ESS compared with segments in arteries with normal microvascular function (average ESS: 1.67 ± 1.04 Pa vs. 2.03 ± 1.72 Pa [p = 0.050]; lowest ESS: 0.54 ± 0.25 Pa vs. 0.72 ± 0.32 Pa [p = 0.014]). Coronary segments in arteries with abnormal epicardial endothelial function also exhibited significantly lower ESS compared with segments in arteries with normal epicardial function (average ESS: 1.49 ± 0.89 Pa vs. 1.93 ± 1.50 Pa [p < 0.0001]; low ESS: 1.26 ± 0.81 Pa vs. 1.56 ± 1.30 Pa [p = 0.001]; lowest ESS: 0.51 ± 0.27 Pa vs. 0.65 ± 0.29 Pa [p = 0.080]). Patients with abnormal microvascular endothelialfunction exhibited a progressive decrease in average and low ESS, starting from patients with normal epicardial endothelial function to those with both microvascular and epicardial endothelial dysfunction (p < 0.0001 and p = 0.004, respectively). CONCLUSIONS: These data indicate an association between dysfunction of the microvascular and epicardial endothelium and local ESS at the early stages of coronary atherosclerosis in humans. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
KEYWORDS: atherosclerosis; coronary artery disease; endothelial function; endothelial shear stress; endothelium; microvascular disease
J Appl Physiol. 2018 May 10. doi: 10.1152/japplphysiol.00086.2018. [Epub ahead of print]
Reversing age-associated arterial dysfunction: insight from preclinical models.
Gogulamudi VR1, Cai J2, Lesniewski LA3.
Author information 1Division of Geriatrics, University of Utah, United States.2Internal Medicine-Division of Geriatrics, University of Utah.3Internal Medicine-Division of Geriatrics, University of Utah, United States. Corresponding Author; E-mail Address: email@example.com
Abstract Cardiovascular diseases (CVDs) remain the leading causes of death in the US, and advancing age is a primary risk factor. Impaired endothelium dependent dilation and increased stiffening of the arteries with aging are independent predictors of CVD. Increased tissue and systemic oxidative stress and inflammation underlie this age-associated arterial dysfunction. Calorie restriction (CR) is the most powerful intervention known to increase lifespan and improve age-related phenotypes, including arterial dysfunction. However, the translatability of long term CR to clinical populations is limited, stimulating interest in the pursuit of pharmacological CR mimetics to reproduce the beneficial effects of CR. The energy sensing pathways, mammalian target of rapamycin (mTOR), adenosine monophosphate protein kinase (AMPK), and sirtuin-1 (Sirt-1) have all been implicated in the beneficial effects of CR on longevity and/or physiological function and, as such, have emerged as potential targets for therapeutic intervention as CR mimetics. Although manipulation of each of these pathways has CR-like benefits on arterial function, the magnitude and/or mechanisms can be disparate from that of CR. Nevertheless, targeting these pathways in older individuals may provide some benefits against arterial dysfunction and CVD in older adults. The goal of this review is to provide a brief discussion of the mechanisms and pathways underlying age-associated dysfunction in large arteries, how these are impacted by CR and to present the available evidence suggesting that targeting energy sensing pathways as vascular CR mimetics.
KEYWORDS: AMPK; Sirt-1; aging; arterial dysfunction; mTOR Angiology. 2018 Jan 1:3319718774660. doi: 10.1177/0003319718774660. [Epub ahead of print] Total Hip Replacement Provokes Endothelial Dysfunction. Poredos P1, Mavric A2, Leben L2, Poredos P2, Jezovnik MK3. Author information 11 Department of Anaesthesiology and Perioperative Intensive Care, University Medical Centre Ljubljana, Ljubljana, Slovenia.22 Department of Vascular Disease, University Medical Centre Ljubljana, Ljubljana, Slovenia.33 Department of Advanced Cardiopulmonary Therapies and Transplantation, The University of Texas Health Science Center at Houston, Houston, USA. Abstract Surgery represents an increased risk of different perioperative complications. Endothelial function (EF) is a key mechanism responsible for cardiovascular homeostasis and is involved in thromboembolic complications. We aimed to follow changes of EF in an early postoperative period in patients undergoing total hip replacement (THR). Endothelial function was assessed noninvasively in 70 consecutive patients who underwent an elective THR under spinal anesthesia. Flow-mediated dilation (FMD) and low flow-mediated constriction capability of the brachial artery, which are indicators of EF were measured before the operation (baseline), 24 hours after the operative procedure, and 5 to 7 days postoperatively. Baseline FMD was 12.3% and decreased a day after surgery to 7.3% ( P < .001). After 5 to 7 days, it gradually increased to 9.2%. However, on average, it was lower than before surgery ( P < .001). The median duration of THR was 85.0 (65.0-100.0) minutes, the average hospital length of stay was 7 days. Total hip replacement is associated with an immediate decrease in FMD which remains significantly decreased 5 to 7 days after the surgery compared with the preoperative value. These results indicate that surgery provokes endothelial dysfunction and deteriorates cardiovascular homeostasis. This effect could be involved in cardiovascular complications in the postoperative period. KEYWORDS: cardiovascular complications; endothelial dysfunction; perioperative stress response; total hip replacement
Curr Hypertens Rep. 2018 May 7;20(5):44. doi: 10.1007/s11906-018-0835-5.
Modulation of Vascular Reactivity by Perivascular Adipose Tissue (PVAT). Agabiti-Rosei C1,2, Paini A3, De Ciuceis C3, Withers S4, Greenstein A4, Heagerty AM4, Rizzoni D3. Author information 1Department of Medicine, Manchester University, Manchester, UK. firstname.lastname@example.orgClinica Medica, Department of Medical and Surgical Sciences, University of Brescia, c/o 2a Medicina Spedali Civili di Brescia, Piazza Spedali Civili 1, 25100, Brescia, Italy. email@example.comClinica Medica, Department of Medical and Surgical Sciences, University of Brescia, c/o 2a Medicina Spedali Civili di Brescia, Piazza Spedali Civili 1, 25100, Brescia, Italy.4Department of Medicine, Manchester University, Manchester, UK. Abstract PURPOSE OF REVIEW: In this review, we discuss the role of perivascular adipose tissue (PVAT) in the modulation of vascular contractility and arterial pressure, focusing on the role of the renin-angiotensin-aldosterone system and oxidative stress/inflammation. RECENT FINDINGS: PVAT possesses a relevant endocrine-paracrine activity, which may be altered in several pathophysiological and clinical conditions. During the last two decades, it has been shown that PVAT may modulate vascular reactivity. It has also been previously demonstrated that inflammation in adipose tissue may be implicated in vascular dysfunction. In particular, adipocytes secrete a number of adipokines with various functions, as well as several vasoactive factors, together with components of the renin-angiotensin system which may act at local or at systemic level. It has been shown that the anti-contractile effect of PVAT is lost in obesity, probably as a consequence of the development of adipocyte hypertrophy, inflammation, and oxidative stress. Adipose tissue dysfunction is interrelated with inflammation and oxidative stress, thus contributing to endothelial dysfunction observed in several pathological and clinical conditions such as obesity and hypertension. Decreased local adiponectin level, macrophage recruitment and infiltration, and activation of renin-angiotensin-aldosterone system could play an important role in this regard. KEYWORDS: Hypoxia; Melatonin; Oxidative stress; Perivascular adipose tissue; Small arteries