Endothelial Function
2002; Lippincott Williams & Wilkins; Volume: 106; Issue: 6 Linguagem: Inglês
10.1161/01.cir.0000028581.07992.56
ISSN1524-4539
AutoresJoseph A. Vita, John F. Keaney,
Tópico(s)Antioxidant Activity and Oxidative Stress
ResumoHomeCirculationVol. 106, No. 6Endothelial Function Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBEndothelial FunctionA Barometer for Cardiovascular Risk? Joseph A. Vita and John F. KeaneyJr Joseph A. VitaJoseph A. Vita From Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Mass. and John F. KeaneyJrJohn F. KeaneyJr From Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Mass. Originally published6 Aug 2002https://doi.org/10.1161/01.CIR.0000028581.07992.56Circulation. 2002;106:640–642The endothelium regulates vascular homeostasis by elaborating a variety of paracrine factors that act locally in the blood vessel wall and lumen.1 Under normal conditions, the sum total effect of these endothelial factors is to maintain normal vascular tone, blood fluidity, and limit vascular inflammation and smooth muscle cell proliferation. However, when coronary risk factors are present, the endothelium may adopt a phenotype that facilitates inflammation, thrombosis, vasoconstriction, and atherosclerotic lesion formation.2 In human subjects, this maladaptive endothelial phenotype manifests itself prior to the development of frank atherosclerosis and is associated with traditional risk factors such as hypercholesterolemia, hypertension, and diabetes mellitus and with emerging risk factors such as hyperhomocystinemia, obesity, and systemic inflammation.1See p 653In addition to its role in early atherosclerosis, there is growing recognition that endothelial dysfunction also contributes to the later stages of the disease when patients develop clinical symptoms. Cross-sectional studies have demonstrated the most severe impairment of endothelial function in arteries containing a culprit lesion that precipitates unstable angina or myocardial infarction.3,4 Furthermore, endothelial dysfunction promotes pathological vasoconstrictor responses in situations known to provoke ischemia, including physical and emotional stress.5 Another line of evidence supporting the pathophysiological role of endothelial dysfunction is provided by intervention studies.6 The ability to improve endothelial function is a common feature of many otherwise diverse interventions proven to reduce cardiovascular risk. For example, lipid-lowering therapy, angiotensin-converting enzyme inhibitors, smoking cessation, and physical exercise have all been shown to reduce cardiovascular risk and to improve endothelium-dependent vasodilation in the coronary and peripheral circulations.1In the past, most of the evidence suggesting a causal relation between endothelial dysfunction and clinical events from atherosclerosis was circumstantial. Recently, this evidence has been strengthened by a series of outcome studies showing that endothelial dysfunction predicts future events. For example, Suwaidi and colleagues7 examined 157 patients with mild coronary disease and demonstrated a greater incidence of cardiovascular events during 2.3 year follow-up in patients with impaired endothelium-dependent vasodilation of coronary resistance and conduit arteries. A similar study by Schachinger and colleagues8 examined coronary artery vasomotor responses to acetylcholine and nitroglycerin infusions, increased flow, and the cold pressor test in 147 patients with coronary artery disease and then followed them for a median of 7.7 years. Patients with more severe impairment of endothelium-dependent and endothelium-independent vasodilator function were more likely to suffer an event. Those two studies are limited by the relatively small number of clinical events (6 and 16, respectively) and the inclusion of coronary revascularization procedures as events. Nevertheless, they are quite important because they provided the first evidence that endothelial dysfunction has prognostic value.In the present issue of Circulation, Halcox and colleagues9 provide additional information about the predictive value of coronary endothelial dysfunction. In the largest study of this type to date, they examined the coronary blood flow and epicardial coronary diameter responses to endothelium-dependent and endothelium-independent vasodilators in 308 patients undergoing cardiac catheterization. During an average 46-month follow-up period, they observed a total of 35 ischemic cardiovascular events, including sudden cardiac death, acute myocardial infarction, unstable angina, and stroke. These events were independently associated with impaired endothelium-dependent dilation of both coronary microvessels and epicardial arteries, even after controlling for other clinical variables such as the presence of coronary disease and traditional risk factors. In contrast, vasodilator responses to the endothelium-independent vasodilators sodium nitroprusside and adenosine did not predict events, providing evidence for a specific relation with endothelial dysfunction. The results were similar when an additional 21 patients who required a coronary revascularization procedure were also categorized as having an event. Very interestingly, impaired endothelium-dependent vasodilation predicted cardiovascular events even in patients with angiographically normal coronary arteries.Thus, the study by Halcox and colleagues9 makes an important contribution to the literature on endothelial function. Together with the prior studies by Suwaidi7 and Schachinger,8 it makes a very strong case that impaired vascular function in the coronary circulation relates to the pathogenesis of cardiovascular disease. The strengths of the study include its large sample size, the well-developed methodology for study of coronary endothelial function, and the focus on spontaneously occurring cardiovascular disease events. The study by Halcox and colleagues has several limitations, as acknowledged by the authors.9 For example, the study was retrospective in nature. The investigators apparently contacted and obtained clinical information from patients who had undergone study of coronary vascular function for other reasons in their laboratory over recent years. The study also excluded patients with relatively severe coronary disease, and thus is not applicable to all patients.Although assessment of coronary endothelial function is clearly germane for coronary artery disease events, this methodology is limited by the risk and expense of coronary angiography and selective intracoronary agonist infusion. As a consequence, there has been considerable interest in the study of endothelial vasomotor function in more accessible vascular beds, such as the brachial circulation. Many investigators have used venous occlusion plethysmography to examine vasomotor responses of forearm resistance vessels during brachial artery infusion of acetylcholine and other endothelium-dependent vasodilators.10 This approach affords several advantages including the ability to examine dose-response relations and use specific agonists and antagonists. However, these studies are limited by the requirement for arterial catheterization that renders them less well suited for large-scale and intervention studies. An alternative approach involves vascular ultrasound to examine endothelium-dependent flow-mediated dilation of the conduit brachial artery.11 This noninvasive technique has gained popularity as an assessment of endothelial function that can safely be applied to large and varied groups of patients that may involve repeated measurement of vascular function over time. Similar to the coronary circulation, endothelial function in the brachial circulation is impaired in the setting of traditional and novel risk factors and responds to interventions known to reduce cardiovascular disease risk.1The relevance of the brachial circulation to coronary and carotid artery events is not obvious. However, the systemic nature of many risk factors makes it plausible that they might affect central and peripheral arteries in a parallel manner. Indeed, studies suggest that endothelial dysfunction detected noninvasively in the arm correlates with coronary endothelial dysfunction.12 Despite these findings, it is well recognized that physiological mechanisms differ importantly according to vascular bed. Although the brachial artery does develop atherosclerosis,13 it is clinically different from the obstructive disease that affects the coronary circulation. For these reasons, there has been a need for outcome studies demonstrating the clinical relevance of endothelial dysfunction in brachial circulation.Several recent studies have examined this question using both the invasive and noninvasive approaches. Perticone and colleagues14 observed that an impaired forearm blood flow response to acetylcholine predicted future cardiovascular events in patients with hypertension. Heitzer and colleagues15 observed a similar relationship in patients with coronary artery disease. In regard to ultrasound-detected flow-mediated dilation, Neunteufl and colleagues16 observed a relation between endothelial dysfunction and need for a revascularization procedure, although their study had a relatively small number of subjects and the relation between endothelial dysfunction and events was lost after controlling for extent of coronary disease. A very recent prospective study from our laboratory demonstrated that impaired brachial artery flow-mediated dilation is an independent predictor of short-term events in high-risk patients undergoing surgery for vascular disease.17Thus, assessment of endothelial function in both the coronary and peripheral circulation of patients with cardiovascular disease and coronary risk factors provides prognostic information about future cardiovascular disease events. This body of clinical evidence fits well with current paradigms depicting the endothelium as an organ that integrates signals between the milieu of the vascular wall and the vessel lumen. In this context, endothelial function should represent an excellent "barometer" of underlying vascular health as it represents an orchestrated response to the many known and unknown processes that contribute to the development, progression, and clinical expression of atherosclerosis. Indeed, it is plausible that endothelial resistance to the adverse effects of risk factors might be determined by genetic or environmental factors that are currently difficult to quantify using traditional risk assessment models.Although the present body of knowledge supports the notion that endothelial function has prognostic value for cardiovascular risk, several important issues remain unaddressed. Most of the published data involves selected patient populations referred for evaluation of cardiovascular disease or with established risk factors for the disease. Thus, the extent to which these data are applicable to the general population remains to be determined. Moreover, clinical studies to date have been largely retrospective and applied a variety of methods to assess endothelial function, thereby precluding consensus estimates for positive and negative predictive value. These issues are critical for any future plans to use endothelial function as a surrogate marker for cardiovascular risk to effectively target individuals for intensive primary prevention and assess potential new therapies. Further prospective studies involving large numbers of patients will be required to resolve these issues and determine the most clinically useful vascular bed and methodology for assessment of endothelial function.The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.Drs Vita and Keaney and their work on endothelial function are supported in part by a Program Project Grant from the National Institutes of Health (PO1HL60886) and by NIH grants P50 HL55993 (J.A.V.), HL/AI64753 (J.A.V., J.F.K.), and HL60040 (J.A.V., J.F.K.).FootnotesCorrespondence to Joseph A. Vita, MD, Section of Cardiology, Boston Medical Center, 88 East Newton St, Boston, MA 02118. E-mail [email protected] References 1 Gokce N, Keaney JF Jr, Vita JA. Endotheliopathies: clinical manifestations of endothelial dysfunction. In: Loscalzo J, Shafer AI, eds. Thrombosis and Hemorrhage. Baltimore, Md: Williams and Wilkins; 1998:901–924.Google Scholar2 Levine GN, Keaney JF Jr, Vita JA. Cholesterol reduction in cardiovascular disease: clinical benefits and possible mechanisms. N Engl J Med. 1995; 332: 512–521.CrossrefMedlineGoogle Scholar3 Okumura K, Yasue H, Matsuyama K, et al. Effect of acetylcholine on the highly stenotic coronary artery: difference between the constrictor response of the infarct-related coronary artery and that of the noninfarct-related artery. J Am Coll Cardiol. 1992; 19: 752–758.CrossrefMedlineGoogle Scholar4 Bogaty P, Hackett D, Davies G, et al. Vasoreactivity of the culprit lesion in unstable angina. Circulation. 1994; 90: 5–11.CrossrefMedlineGoogle Scholar5 Yeung AC, Vekshtein VI, Krantz DS, et al. The effect of atherosclerosis on the vasomotor response of coronary arteries to mental stress. N Engl J Med. 1991; 325: 1551–1556.CrossrefMedlineGoogle Scholar6 Vita JA, Keaney JF Jr. Exercise: toning up the endothelium? N Engl J Med. 2000; 342: 503–505.CrossrefMedlineGoogle Scholar7 Suwaidi JA, Hamasaki S, Higano ST, et al. Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation. 2000; 101: 948–954.CrossrefMedlineGoogle Scholar8 Schachinger V, Britten MB, Zeiher AM. Prognostic impact of coronary vasodilator dysfunction on adverse long- term outcome of coronary heart disease. Circulation. 2000; 101: 1899–1906.CrossrefMedlineGoogle Scholar9 Halcox JPJ, Schenke WH, Zalos G, et al. Prognostic value of coronary vascular endothelial function. 2002; 106: 653–658.Google Scholar10 Creager MA, Cooke JP, Mendelsohn ME, et al. Impaired vasodilation of forearm resistance vessels in hypercholesterolemic humans. J Clin Invest. 1990; 86: 228–234.CrossrefMedlineGoogle Scholar11 Corretti MC, Anderson TJ, Benjamin EJ, et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol. 2002; 39: 257–265.CrossrefMedlineGoogle Scholar12 Anderson TJ, Uehata A, Gerhard MD, et al. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol. 1995; 26: 1235–1241.CrossrefMedlineGoogle Scholar13 Sorensen KE, Kristensen IB, Celermajer DS. Atherosclerosis in the human brachial artery. J Am Coll Cardiol. 1997; 29: 318–322.CrossrefMedlineGoogle Scholar14 Perticone F, Ceravolo R, Pujia A, et al. Prognostic significance of endothelial dysfunction in hypertensive patients. Circulation. 2001; 104: 191–196.CrossrefMedlineGoogle Scholar15 Heitzer T, Schlinzig T, Krohn K, et al. Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation. 2001; 104: 2673–2678.CrossrefMedlineGoogle Scholar16 Neunteufl T, Heher S, Katzenschlager R, et al. Late prognostic value of flow-mediated dilation in the brachial artery of patients with chest pain. Am J Cardiol. 2000; 86: 207–210.CrossrefMedlineGoogle Scholar17 Gokce N, Keaney JF Jr, Menzoian JO, et al. Risk stratification for postoperative cardiovascular events via noninvasive assessment of endothelial function. Circulation. 2002; 105: 1567–1572.LinkGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetailsCited By Marcinek A, Katarzynska J, Sieron L, Skokowski R, Zielinski J and Gebicki J (2023) Non-Invasive Assessment of Vascular Circulation Based on Flow Mediated Skin Fluorescence (FMSF), Biology, 10.3390/biology12030385, 12:3, (385) Sabouri M, Amirshaghaghi F and Hesari M (2023) High-intensity interval training improves the vascular endothelial function comparing moderate-intensity interval training in overweight or obese adults: A meta-analysis, Clinical Nutrition ESPEN, 10.1016/j.clnesp.2022.11.023, 53, (100-106), Online publication date: 1-Feb-2023. Liu Y, Chen J, Liang H, Cai Y, Li X, Yan L, Zhou L, Shan L and Wang H (2022) Human umbilical cord-derived mesenchymal stem cells not only ameliorate blood glucose but also protect vascular endothelium from diabetic damage through a paracrine mechanism mediated by MAPK/ERK signaling, Stem Cell Research & Therapy, 10.1186/s13287-022-02927-8, 13:1, Online publication date: 1-Dec-2022. Patel S, Shokr H, Greenstein A and Gherghel D (2022) Macro- and Microvascular Function in Middle-Aged Individuals with Low Cardiovascular Disease Risk, Journal of Clinical Medicine, 10.3390/jcm11236962, 11:23, (6962) Seshadri S, Shokr H and Gherghel D (2022) Retinal Microvascular Abnormalities and Systemic Arterial Stiffness Are the First Manifestation of Cardiovascular Abnormalities in Patients with Untreated Moderate to Severe Obstructive Sleep Apnoea and with Low to Intermediate Cardiovascular Risk—A Pilot Study, Biomedicines, 10.3390/biomedicines10102669, 10:10, (2669) Ai S, Li Z, Wang S, Chen S, Chan J, Au C, Bao Y, Li A, Zhang J, Chan K and Wing Y (2022) Blood pressure and childhood obstructive sleep apnea: A systematic review and meta-analysis, Sleep Medicine Reviews, 10.1016/j.smrv.2022.101663, 65, (101663), Online publication date: 1-Oct-2022. Bryan N, Burleigh M and Easton C (2022) The oral microbiome, nitric oxide and exercise performance, Nitric Oxide, 10.1016/j.niox.2022.05.004, 125-126, (23-30), Online publication date: 1-Aug-2022. Triggle C, Mohammed I, Bshesh K, Marei I, Ye K, Ding H, MacDonald R, Hollenberg M and Hill M (2022) Metformin: Is it a drug for all reasons and diseases?, Metabolism, 10.1016/j.metabol.2022.155223, 133, (155223), Online publication date: 1-Aug-2022. Morishima T, Iemitsu M, Fujie S and Ochi E (2022) Prior beetroot juice ingestion offsets endothelial dysfunction following prolonged sitting, Journal of Applied Physiology, 10.1152/japplphysiol.00200.2022, 133:1, (69-74), Online publication date: 1-Jul-2022. Shahdadian S, Wang X, Kang S, Carter C, Chaudhari A and Liu H (2022) Prefrontal cortical connectivity and coupling of infraslow oscillation in the resting human brain: a 2-channel broadband NIRS study, Cerebral Cortex Communications, 10.1093/texcom/tgac033, 3:3, Online publication date: 1-Jul-2022. Bonanni M, Rehak L, Massaro G, Benedetto D, Matteucci A, Russo G, Esperto F, Federici M, Mauriello A and Sangiorgi G (2022) Autologous Immune Cell-Based Regenerative Therapies to Treat Vasculogenic Erectile Dysfunction: Is the Immuno-Centric Revolution Ready for the Prime Time?, Biomedicines, 10.3390/biomedicines10051091, 10:5, (1091) Wang R, Guo Y, Li L, Luo M, Peng L, Lv D, Cheng Z, Xue Q, Wang L and Huang J (2022) Role of thioredoxin-interacting protein in mediating endothelial dysfunction in hypertension, Genes & Diseases, 10.1016/j.gendis.2020.08.008, 9:3, (753-765), Online publication date: 1-May-2022. Emamat H, Mousavi S, Kargar Shouraki J, Hazrati E, Mirghazanfari S, Samizadeh E, Hosseini M, Hadi V and Hadi S (2022) The effect of Nigella sativa oil on vascular dysfunction assessed by flow‐mediated dilation and vascular‐related biomarkers in subject with cardiovascular disease risk factors: A randomized controlled trial , Phytotherapy Research, 10.1002/ptr.7441, 36:5, (2236-2245), Online publication date: 1-May-2022. Fernández-Rubio H, Becerro-de-Bengoa-Vallejo R, Rodríguez-Sanz D, Calvo-Lobo C, Vicente-Campos D and Chicharro J (2022) Exercise Training and Interventions for Coronary Artery Disease, Journal of Cardiovascular Development and Disease, 10.3390/jcdd9050131, 9:5, (131) Minhas A, Goerlich E, Corretti M, Arbab-Zadeh A, Kelle S, Leucker T, Lerman A and Hays A (2022) Imaging Assessment of Endothelial Function: An Index of Cardiovascular Health, Frontiers in Cardiovascular Medicine, 10.3389/fcvm.2022.778762, 9 Qiu Y, Chao C, Jiang L, Zhang J, Niu Q, Guo Y, Song Y, Li P, Zhu M and Yin Y (2022) Citronellal alleviate macro- and micro-vascular damage in high fat diet / streptozotocin - Induced diabetic rats via a S1P/S1P1 dependent signaling pathway, European Journal of Pharmacology, 10.1016/j.ejphar.2022.174796, 920, (174796), Online publication date: 1-Apr-2022. Li R, Wang L, Liu S, Duan H, Zhang Q, Zhang T, Peng W, Huang Y and Wu C (2022) Natural Flavonoids Derived From Fruits Are Potential Agents Against Atherosclerosis, Frontiers in Nutrition, 10.3389/fnut.2022.862277, 9 Liu Y, Luo X, Jia H and Yu B (2022) The Effect of Blood Pressure Variability on Coronary Atherosclerosis Plaques, Frontiers in Cardiovascular Medicine, 10.3389/fcvm.2022.803810, 9 Su E, Yu P, Zhang B, Zhang A, Xie S, Zhang C, Li S, Zou Y, Liu M, Jiang H and Ge J (2022) Endothelial Intracellular ANG (Angiogenin) Protects Against Atherosclerosis by Decreasing Endoplasmic Reticulum Stress, Arteriosclerosis, Thrombosis, and Vascular Biology, 42:3, (305-325), Online publication date: 1-Mar-2022. Wang X, Ma L, Shahdadian S, Wu A, Truong N and Liu H (2022) Metabolic Connectivity and Hemodynamic-Metabolic Coherence of Human Prefrontal Cortex at Rest and Post Photobiomodulation Assessed by Dual-Channel Broadband NIRS, Metabolites, 10.3390/metabo12010042, 12:1, (42) Schwarz E and Steier J (2022) Herzfunktion bei COPD-Patienten Physiotherapie bei chronisch-obstruktiven Atemwegs- und Lungenerkrankungen, 10.1007/978-3-662-63613-8_12, (131-137), . Jiang W, Blumenthal J, Wang J and Sherwood A (2022) Mental Stress-Induced Myocardial Ischemia: Prevalence, Clinical Significance, and Treatment Implications Handbook of Cardiovascular Behavioral Medicine, 10.1007/978-0-387-85960-6_46, (1107-1130), . Kim Y, Her A, Kim B, Hong S, Ahn C, Kim J, Ko Y, Choi D, Hong M and Jang Y (2021) Impact of preprocedural coronary flow grade on duration of dual antiplatelet therapy in acute myocardial infarction, Scientific Reports, 10.1038/s41598-021-91130-5, 11:1, Online publication date: 1-Dec-2021. Bonanno G, Weiss R, Piccini D, Yerly J, Soleimani S, Pan L, Bi X, Hays A, Stuber M and Schär M (2021) Volumetric coronary endothelial function assessment: a feasibility study exploiting stack‐of‐stars 3D cine MRI and image‐based respiratory self‐gating, NMR in Biomedicine, 10.1002/nbm.4589, 34:11, Online publication date: 1-Nov-2021. Salvatore T, Caturano A, Galiero R, Di Martino A, Albanese G, Vetrano E, Sardu C, Marfella R, Rinaldi L and Sasso F (2021) Cardiovascular Benefits from Gliflozins: Effects on Endothelial Function, Biomedicines, 10.3390/biomedicines9101356, 9:10, (1356) Sakellariou X, Papafaklis M, Domouzoglou E, Katsouras C, Michalis L and Naka K (2021) Exercise-mediated adaptations in vascular function and structure: Beneficial effects in coronary artery disease, World Journal of Cardiology, 10.4330/wjc.v13.i9.399, 13:9, (399-415), Online publication date: 26-Sep-2021. Okada A, Murata T, Matin K, Ariyoshi M, Otsuka R, Yamashita M, Suzuki M, Wakiyama R, Tateno K, Suzuki M, Aoyagi H, Uematsu H, Imamura A, Kosaka M, Mizukaki T, Sato T, Kawahara H, Hanada N and Kielbassa A (2021) Effect of advanced periodontal self-care in patients with early-stage periodontal diseases on endothelial function: An open-label, randomized controlled trial, PLOS ONE, 10.1371/journal.pone.0257247, 16:9, (e0257247) Lubrano V and Balzan S (2021) Status of biomarkers for the identification of stable or vulnerable plaques in atherosclerosis, Clinical Science, 10.1042/CS20210417, 135:16, (1981-1997), Online publication date: 27-Aug-2021. Ugusman A, Kumar J and Aminuddin A (2021) Endothelial function and dysfunction: Impact of sodium-glucose cotransporter 2 inhibitors, Pharmacology & Therapeutics, 10.1016/j.pharmthera.2021.107832, 224, (107832), Online publication date: 1-Aug-2021. Xiao M, Tang Y, Wang S, Wang J, Wang J, Guo Y, Zhang J and Gu J (2021) The Role of Fibroblast Growth Factor 21 in Diabetic Cardiovascular Complications and Related Epigenetic Mechanisms, Frontiers in Endocrinology, 10.3389/fendo.2021.598008, 12 Yang H, Baltzis D, Bhatt V, Haack M, Meier-Ewert H, Gautam S, Veves A and Mullington J (2020) Macro- and microvascular reactivity during repetitive exposure to shortened sleep: sex differences, Sleep, 10.1093/sleep/zsaa257, 44:5, Online publication date: 14-May-2021. Holder S, Bruno R, Shkredova D, Dawson E, Jones H, Hopkins N, Hopman M, Bailey T, Coombes J, Askew C, Naylor L, Maiorana A, Ghiadoni L, Thompson A, Green D and Thijssen D (2021) Reference Intervals for Brachial Artery Flow-Mediated Dilation and the Relation With Cardiovascular Risk Factors, Hypertension, 77:5, (1469-1480), Online publication date: 1-May-2021. Emamat H, Asadian S, Zahedmehr A, Ghanavati M and Nasrollahzadeh J (2020) The effect of barberry ( Berberis vulgaris ) consumption on flow‐mediated dilation and inflammatory biomarkers in patients with hypertension: A randomized controlled trial , Phytotherapy Research, 10.1002/ptr.7000, 35:5, (2607-2615), Online publication date: 1-May-2021. Adamczyk A, Matuszyk E, Radwan B, Rocchetti S, Chlopicki S and Baranska M (2021) Toward Raman Subcellular Imaging of Endothelial Dysfunction, Journal of Medicinal Chemistry, 10.1021/acs.jmedchem.1c00051, 64:8, (4396-4409), Online publication date: 22-Apr-2021. Sangiorgi G, Cereda A, Benedetto D, Bonanni M, Chiricolo G, Cota L, Martuscelli E and Greco F (2021) Anatomy, Pathophysiology, Molecular Mechanisms, and Clinical Management of Erectile Dysfunction in Patients Affected by Coronary Artery Disease: A Review, Biomedicines, 10.3390/biomedicines9040432, 9:4, (432) Rovella V, Rodia G, Di Daniele F, Cardillo C, Campia U, Noce A, Candi E, Della-Morte D and Tesauro M (2021) Association of Gut Hormones and Microbiota with Vascular Dysfunction in Obesity, Nutrients, 10.3390/nu13020613, 13:2, (613) Begum M, Konja D, Singh S, Chlopicki S and Wang Y (2021) Endothelial SIRT1 as a Target for the Prevention of Arterial Aging: Promises and Challenges, Journal of Cardiovascular Pharmacology, 10.1097/FJC.0000000000001154, 78:6S, (S63-S77) Yang Y, Dong J, Cui R, Muraki I, Yamagishi K, Sawada N, Iso H and Tsugane S (2020) Consumption of flavonoid-rich fruits and risk of CHD: a prospective cohort study, British Journal of Nutrition, 10.1017/S0007114520001993, 124:9, (952-959), Online publication date: 14-Nov-2020. Semenova Y, Karpov A, Takhauov R, Milto I, Shanina E, Kovalchuk E and Suslova T (2020) Markers of endothelial dysfunction in patients with arterial hypertension exposed to occupational irradiation of low intensity, Kardiologiia, 10.18087/cardio.2020.10.n1236, 60:10, (73-79) KIŞ M, SOYDAN E, TATLI KIŞ T and HAKVERDİ G (2020) Koroner arter hastalığında HbA1c düzeyi ile endotel fonksiyonları arasındaki ilişki, Bozok Tıp Dergisi, 10.16919/bozoktip.793119 Hoong C, Tan M, Kao S and Khoo E (2020) Effects of external counter-pulsation on endothelial function assessed by peripheral artery tonometry, levels of glycaemia and metabolic markers in individuals with type 2 diabetes mellitus, Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 10.1016/j.dsx.2020.11.003, 14:6, (2139-2145), Online publication date: 1-Nov-2020. Craighead D, Freeberg K and Seals D (2020) Vascular Endothelial Function in Midlife/Older Adults Classified According to 2017 American College of Cardiology/American Heart Association Blood Pressure Guidelines, Journal of the American Heart Association, 9:17, Online publication date: 1-Sep-2020.Lavin Plaza B, Phinikaridou A, Andia M, Potter M, Lorrio S, Rashid I and Botnar R (2020) Sustained Focal Vascular Inflammation Accelerates Atherosclerosis in Remote Arteries, Arteriosclerosis, Thrombosis, and Vascular Biology, 40:9, (2159-2170), Online publication date: 1-Sep-2020. Daiber A and Chlopicki S (2020) Revisiting pharmacology of oxidative stress and endothelial dysfunction in cardiovascular disease: Evidence for redox-based therapies, Free Radical Biology and Medicine, 10.1016/j.freeradbiomed.2020.02.026, 157, (15-37), Online publication date: 1-Sep-2020. Gustafson D, Raju S, Wu R, Ching C, Veitch S, Rathnakumar K, Boudreau E, Howe K and Fish J (2020) Overcoming Barriers, Arteriosclerosis, Thrombosis, and Vascular Biology, 40:8, (1818-1829), Online publication date: 1-Aug-2020. Lee S, Ribeiro L, Martin D, Zwart S, Feiveson A, Laurie S, Macias B, Crucian B, Krieger S, Weber D, Grune T, Platts S, Smith S and Stenger M (2020) Arterial structure and function during and after long-duration spaceflight, Journal of Applied Physiology, 10.1152/japplphysiol.00550.2019, 129:1, (108-123), Online publication date: 1-Jul-2020. Servient
Referência(s)