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Short Communication
Clinical Diabetes & Therapeutics
Three Months Monitored Metabolic Fitness Modulates Cardiovascular Risk Factors in Diabetic Patients
Ilenia Cirilli, Sonia Silvestri, Fabio Marcheggiani, Fabiola Olivieri, Roberta Galeazzi, Roberto Antonicelli, Rina Recchioni, Fiorella Marcheselli, Tiziana Bacchetti, Luca Tiano, Patrick Orlando
Diabetes Metab J. 2019;43(6):893-897.   Published online June 27, 2019
DOI: https://doi.org/10.4093/dmj.2018.0254
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  • 8 Web of Science
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AbstractAbstract PDFPubReader   

Cardiovascular diseases represent the leading cause of death and moderate physical exercise is associated with a reduction in cardiovascular risk. The aim of the study was to evaluate the correlation between the amount of exercise recorded daily by a wearable gravitometer for 3 months and selected biochemical and clinical parameters. Nineteen sedentary type 2 diabetics were recruited and distributed into three homogenous groups, low, medium, and high exercise, according to the level of physical exercise monitored and expressed as MOVEs. Data showed an inverse correlation between MOVEs and oxidative stress indexes and a significant improvement in paraoxonase-1 activities and endothelial functionality. Decrease of visceral/total adipose tissue ratio, systolic blood pressure and a down-regulation of the inflammatory microRNA-146a in high exercise group were observed. Finally, a decrease of glycosylated hemoglobin and an up-regulation of the angiogenic microRNA-130a in medium exercise one was obtained. In this study, precise daily monitoring permitted to underline the importance of the amount of physical activity to counteract some cardiovascular risk factors persisting in diabetes. Finally, it identifies new microRNA biomarkers for future investigation on the same topic.

Citations

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    Dharmsheel Shrivastav, Desh Deepak Singh
    World Journal of Clinical Cases.2024; 12(3): 525.     CrossRef
  • Is It Possible to Train the Endothelium?—A Narrative Literature Review
    Karolina Biernat, Natalia Kuciel, Justyna Mazurek, Katarzyna Hap
    Life.2024; 14(5): 616.     CrossRef
  • The Effect of Physical Activity/Exercise on miRNA Expression and Function in Non-Communicable Diseases—A Systematic Review
    Moomna Afzal, Francesca Greco, Federico Quinzi, Francesca Scionti, Samantha Maurotti, Tiziana Montalcini, Annamaria Mancini, Pasqualina Buono, Gian Pietro Emerenziani
    International Journal of Molecular Sciences.2024; 25(13): 6813.     CrossRef
  • Effects of Seven Weeks of Combined Physical Training on High-Density Lipoprotein Functionality in Overweight/Obese Subjects
    Tiziana Bacchetti, Camilla Morresi, Gianna Ferretti, Anders Larsson, Torbjörn Åkerfeldt, Michael Svensson
    Metabolites.2023; 13(10): 1068.     CrossRef
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    Juan Gao, Xue Pan, Guoping Li, Emeli Chatterjee, Junjie Xiao
    Journal of Cardiovascular Translational Research.2022; 15(3): 604.     CrossRef
  • Effects of Exercise Training on the Paracrine Function of Circulating Angiogenic Cells
    William S. Evans, Ryan M. Sapp, Katherine I. Kim, James M. Heilman, James Hagberg, Steven J. Prior
    International Journal of Sports Medicine.2021; 42(12): 1047.     CrossRef
  • Chronic and Transient Hyperglycemia Induces Changes in the Expression Patterns of IL6 and ADIPOQ Genes and Their Associated Epigenetic Modifications in Differentiating Human Visceral Adipocytes
    Adam Wróblewski, Justyna Strycharz, Ewa Świderska, Aneta Balcerczyk, Janusz Szemraj, Józef Drzewoski, Agnieszka Śliwińska
    International Journal of Molecular Sciences.2021; 22(13): 6964.     CrossRef
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    Jin Hwa Kim
    Diabetes & Metabolism Journal.2020; 44(1): 54.     CrossRef
Reviews
Pathophysiology
Role of NO/VASP Signaling Pathway against Obesity-Related Inflammation and Insulin Resistance
Yu Mi Kang, Francis Kim, Woo Je Lee
Diabetes Metab J. 2017;41(2):89-95.   Published online November 15, 2016
DOI: https://doi.org/10.4093/dmj.2017.41.2.89
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  • 22 Web of Science
  • 20 Crossref
AbstractAbstract PDFPubReader   

Obesity has quickly become a worldwide pandemic, causing major adverse health outcomes such as dyslipidemia, type 2 diabetes mellitus, cardiovascular disease and cancers. Obesity-induced insulin resistance is the key for developing these metabolic disorders, and investigation to understand the molecular mechanisms involved has been vibrant for the past few decades. Of these, low-grade chronic inflammation is suggested as a critical concept in the development of obesity-induced insulin resistance, and the anti-inflammatory effect of nitric oxide (NO) signaling has been reported to be linked to improvement of insulin resistance in multiple organs involved in glucose metabolism. Recently, a body of evidence suggested that vasodilatory-stimulated phosphoprotein (VASP), a downstream mediator of NO signaling plays a crucial role in the anti-inflammatory effect and improvement of peripheral insulin resistance. These preclinical studies suggest that NO/VASP signaling could be an ideal therapeutic target in the treatment of obesity-related metabolic dysfunction. In this review, we introduce studies that investigated the protective role of NO/VASP signaling against obesity-related inflammation and insulin resistance in various tissues.

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    Ping Lu, Cun-Xiu Gao, Fei-Jian Luo, Yu-Ting Huang, Mei-Mei Gao, Yue-Sheng Long
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    Jorly Mejia-Montilla , Nadia Reyna-Villasmil, Andreina Fernández-Ramírez, Eduardo Reyna-Villasmil
    Revista Repertorio de Medicina y Cirugía.2023; 32(3): 218.     CrossRef
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    Amir Hossein Behnoush, Amirmohammad Khalaji, Zahra Shokri Varniab, Afshin Rahbarghazi, Elahe Amini, Aleksandra Klisic
    Endocrine.2023; 84(2): 328.     CrossRef
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    Qing‐Ling Quan, Kyeong‐No Yoon, Ji Su Lee, Eun Ju Kim, Dong Hun Lee
    Photodermatology, Photoimmunology & Photomedicine.2023; 39(6): 573.     CrossRef
  • Beneficial Metabolic Effects of Praliciguat, a Soluble Guanylate Cyclase Stimulator, in a Mouse Diet-Induced Obesity Model
    Chad D. Schwartzkopf, John R. Hadcock, Guang Liu, Peter Germano, Julien Roux, Courtney M. Shea, Emmanuel S. Buys, Juli E. Jones
    Frontiers in Pharmacology.2022;[Epub]     CrossRef
  • Type 2 Diabetes Complicated With Heart Failure: Research on Therapeutic Mechanism and Potential Drug Development Based on Insulin Signaling Pathway
    Hui Ye, Yanan He, Chuan Zheng, Fang Wang, Ming Yang, Junzhi Lin, Runchun Xu, Dingkun Zhang
    Frontiers in Pharmacology.2022;[Epub]     CrossRef
  • Effect of low-dose tadalafil once daily on glycemic control in patients with type 2 diabetes and erectile dysfunction: a randomized, double-blind, placebo-controlled pilot study
    Min-Kyung Lee, Jae-Hyuk Lee, Seo-Young Sohn, Seo Yeon Lee, Tae-Yoong Jeong, Sae Chul Kim
    Diabetology & Metabolic Syndrome.2022;[Epub]     CrossRef
  • In situ hydrogel capturing nitric oxide microbubbles accelerates the healing of diabetic foot
    Yingzheng Zhao, Lanzi Luo, Lantian Huang, Yingying Zhang, Mengqi Tong, Hanxiao Pan, Jianxun Shangguan, Qing Yao, Shihao Xu, Helin Xu
    Journal of Controlled Release.2022; 350: 93.     CrossRef
  • Amelioration effect of black seed oil against high‐fat diet‐induced obesity in rats through Nrf2/HO‐1 pathway
    Nada F. Abo El‐Magd, Mohamed El‐Mesery, Amro El‐Karef, Mamdouh M. El‐Shishtawy
    Journal of Food Biochemistry.2021;[Epub]     CrossRef
  • An exploratory, randomised, placebo-controlled, 14 day trial of the soluble guanylate cyclase stimulator praliciguat in participants with type 2 diabetes and hypertension
    John P. Hanrahan, Jelena P. Seferovic, James D. Wakefield, Phebe J. Wilson, Jennifer G. Chickering, Joon Jung, Kenneth E. Carlson, Daniel P. Zimmer, Andrew L. Frelinger, Alan D. Michelson, Linda Morrow, Michael Hall, Mark G. Currie, G. Todd Milne, Albert
    Diabetologia.2020; 63(4): 733.     CrossRef
  • Advantages of Phosphodiesterase Type 5 Inhibitors in the Management of Glucose Metabolism Disorders: A Clinical and Translational Issue
    Cristina Antinozzi, Paolo Sgrò, Luigi Di Luigi
    International Journal of Endocrinology.2020; 2020: 1.     CrossRef
  • Association of endothelial dysfunction with incident prediabetes, type 2 diabetes and related traits: the KORA F4/FF4 study
    Marie-Theres Huemer, Cornelia Huth, Florian Schederecker, Stefanie J Klug, Christa Meisinger, Wolfgang Koenig, Wolfgang Rathmann, Annette Peters, Barbara Thorand
    BMJ Open Diabetes Research & Care.2020; 8(1): e001321.     CrossRef
  • Embelin from Embelia ribes ameliorates oxidative stress and inflammation in high-fat diet-fed obese C57BL/6 mice
    Priyanka Bansal, Uma Bhandari, Sayeed Ahmad
    Pharmacognosy Magazine.2020; 16(5): 443.     CrossRef
  • Weight change is significantly associated with risk of thyroid cancer: A nationwide population-based cohort study
    Hyemi Kwon, Kyung-Do Han, Cheol-Young Park
    Scientific Reports.2019;[Epub]     CrossRef
  • Diabetes and Cancer: Cancer Should Be Screened in Routine Diabetes Assessment
    Sunghwan Suh, Kwang-Won Kim
    Diabetes & Metabolism Journal.2019; 43(6): 733.     CrossRef
  • Antioxidant, antihyperglycemic, and antidiabetic activity of Apis mellifera bee tea
    Janielle da Silva Melo da Cunha, Tamaeh Monteiro Alfredo, Jéssica Maurino dos Santos, Valter Vieira Alves Junior, Luiza Antas Rabelo, Emerson Silva Lima, Ana Paula de Araújo Boleti, Carlos Alexandre Carollo, Edson Lucas dos Santos, Kely de Picoli Souza, M
    PLOS ONE.2018; 13(6): e0197071.     CrossRef
  • Relationship Between Circulating Netrin-1 Concentration, Impaired Fasting Glucose, and Newly Diagnosed Type 2 Diabetes
    Jisook Yim, Gyuri Kim, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Jeong-Ho Kim, Jin Won Cho, Sang-Guk Lee, Yong-ho Lee
    Frontiers in Endocrinology.2018;[Epub]     CrossRef
  • Glycyrrhizin ameliorates high fat diet-induced obesity in rats by activating NrF2 pathway
    Nada F. Abo El-Magd, Mohamed El-Mesery, Amro El-Karef, Mamdouh M. El-Shishtawy
    Life Sciences.2018; 193: 159.     CrossRef
  • cGMP-dependent protein kinase I (cGKI) modulates human hepatic stellate cell activation
    Andras Franko, Marketa Kovarova, Susanne Feil, Robert Feil, Robert Wagner, Martin Heni, Alfred Königsrainer, Marc Ruoß, Andreas K. Nüssler, Cora Weigert, Hans-Ulrich Häring, Stefan Z. Lutz, Andreas Peter
    Metabolism.2018; 88: 22.     CrossRef
Regulation of Muscle Microcirculation in Health and Diabetes
Zhenqi Liu, Seung-Hyun Ko, Weidong Chai, Wenhong Cao
Diabetes Metab J. 2012;36(2):83-89.   Published online April 17, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.2.83
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AbstractAbstract PDFPubReader   

Insulin increases microvascular perfusion and substrate exchange surface area in muscle, which is pivotal for hormone action and substrate exchange, by activating insulin signaling cascade in the endothelial cells to produce nitric oxide. This action of insulin is closely coupled with its metabolic action and type 2 diabetes is associated with both metabolic and microvascular insulin resistance. Muscle microvascular perfusion/volume can be assessed by 1-methylxanthine metabolism, contrast-enhanced ultrasound and positron emission tomography. In addition to insulin, several factors have been shown to recruit muscle microvasculature, including exercise or muscle contraction, mixed meals, glucagon-like peptide 1 and angiotensin II type 1 receptor (AT1R) blocker. On the other hand, factors that cause metabolic insulin resistance, such as inflammatory cytokines, free fatty acids, and selective activation of the AT1R, are capable of causing microvascular insulin resistance. Therapies targeting microvascular insulin resistance may help prevent or control diabetes and decrease the associated cardiovascular morbidity and mortality.

Citations

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  • Cardiovascular aging and the microcirculation of skeletal muscle: using contrast-enhanced ultrasound
    Emily C. Dunford, Jason S. Au, Michaela C. Devries, Stuart M. Phillips, Maureen J. MacDonald
    American Journal of Physiology-Heart and Circulatory Physiology.2018; 315(5): H1194.     CrossRef
  • Direct Activation of Angiotensin II Type 2 Receptors Enhances Muscle Microvascular Perfusion, Oxygenation, and Insulin Delivery in Male Rats
    Fei Yan, Zhaoshun Yuan, Nasui Wang, Robert M Carey, Kevin W Aylor, Li Chen, Xinmin Zhou, Zhenqi Liu
    Endocrinology.2018; 159(2): 685.     CrossRef
  • Long-term high-fat diet induces hippocampal microvascular insulin resistance and cognitive dysfunction
    Zhuo Fu, Jing Wu, Tanseli Nesil, Ming D. Li, Kevin W. Aylor, Zhenqi Liu
    American Journal of Physiology-Endocrinology and Metabolism.2017; 312(2): E89.     CrossRef
  • GLP-1 Receptor Agonist Exenatide Increases Capillary Perfusion Independent of Nitric Oxide in Healthy Overweight Men
    Mark M. Smits, Marcel H.A. Muskiet, Lennart Tonneijck, Mark H.H. Kramer, Michaela Diamant, Daniël H. van Raalte, Erik H. Serné
    Arteriosclerosis, Thrombosis, and Vascular Biology.2015; 35(6): 1538.     CrossRef
  • New insights into insulin action and resistance in the vasculature
    Camila Manrique, Guido Lastra, James R. Sowers
    Annals of the New York Academy of Sciences.2014; 1311(1): 138.     CrossRef
  • Angiotensin-(1–7) Recruits Muscle Microvasculature and Enhances Insulin’s Metabolic Action via Mas Receptor
    Zhuo Fu, Lina Zhao, Kevin W. Aylor, Robert M. Carey, Eugene J. Barrett, Zhenqi Liu
    Hypertension.2014; 63(6): 1219.     CrossRef
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    Camila Manrique, James R. Sowers
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Original Article
Angiotensin II Inhibits Insulin Binding to Endothelial Cells
Su-Jin Oh, Won-Chul Ha, Jee-In Lee, Tae-Seo Sohn, Ji-Hyun Kim, Jung-Min Lee, Sang-Ah Chang, Oak-Kee Hong, Hyun-Shik Son
Diabetes Metab J. 2011;35(3):243-247.   Published online June 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.3.243
  • 4,013 View
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  • 6 Crossref
AbstractAbstract PDFPubReader   
Background

Insulin-mediated glucose uptake in insulin target tissues is correlated with interstitial insulin concentration, rather than plasma insulin concentration. Therefore, insulin delivery to the interstitium of target tissues is very important, and the endothelium may also play an important role in the development of insulin resistance.

Methods

After treating bovine aortic endothelial cells with angiotensin II (ATII), we observed the changes in insulin binding capacity and the amounts of insulin receptor (IR) on the cell membranes and in the cytosol.

Results

After treatment of 10-7M ATII, insulin binding was decreased progressively, up to 60% at 60 minutes (P<0.05). ATII receptor blocker (eprosartan) dose dependently improved the insulin binding capacity which was reduced by ATII (P<0.05). At 200 µM, eprosartan fully restored insulin binding capacity, althogh it resulted in only a 20% to 30% restoration at the therapeutic concentration. ATII did not affect the total amount of IR, but it did reduce the amount of IR on the plasma membrane and increased that in the cytosol.

Conclusion

ATII decreased the insulin binding capacity of the tested cells. ATII did not affect the total amount of IR but did decrease the amount of IR on the plasma membrane. Our data indicate that ATII decreases insulin binding by translocating IR from the plasma membrane to the cytosol. The binding of insulin to IR is important for insulin-induced vasodilation and transendothelial insulin transport. Therefore, ATII may cause insulin resistance through this endothelium-based mechanism.

Citations

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  • Acute, local infusion of angiotensin II impairs microvascular and metabolic insulin sensitivity in skeletal muscle
    Dino Premilovac, Emily Attrill, Stephen Rattigan, Stephen M Richards, Jeonga Kim, Michelle A Keske
    Cardiovascular Research.2019; 115(3): 590.     CrossRef
  • Angiotensin II type 2 receptor inhibits expression and function of insulin receptor in rat renal proximal tubule cells
    Yang Yang, Caiyu Chen, Chunjiang Fu, Zaicheng Xu, Cong Lan, Yongchun Zeng, Zhi Chen, Pedro A. Jose, Ye Zhang, Chunyu Zeng
    Journal of the American Society of Hypertension.2018; 12(2): 135.     CrossRef
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    Vladislav Biel, Jan Novák, Luděk Pluháček, Jiří Špác
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    Juan M. Saavedra
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    Mohamed A. Morsy, Gehan H. Heeba, Magda E. Mahmoud
    European Journal of Pharmacology.2015; 750: 90.     CrossRef
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    Ranganath Muniyappa, Sahzene Yavuz
    Molecular and Cellular Endocrinology.2013; 378(1-2): 59.     CrossRef
Randomized Controlled Trial
Randomized, Open Label, Multicenter Clinical Trial about the Effect of Cilazapril on Vascular Endothelial Function in Patients with Type 2 Diabetes Combined with Hypertension.
Sang Youl Rhee, Jeong Taek Woo, Sei Hyun Baik, Hyoung Woo Lee, In Kyu Lee, Hye Soon Kim, Moon Kyu Lee, Min Ho Shong, Chung Gu Cho, Byoung Hyun Park, Bong Soo Cha, Young Seol Kim
Korean Diabetes J. 2006;30(6):450-458.   Published online November 1, 2006
DOI: https://doi.org/10.4093/jkda.2006.30.6.450
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  • 1 Crossref
AbstractAbstract PDF
BACKGROUND
The angiotensin converting enzyme inhibitor (ACEi) improves the vascular endothelial cell function and has a better clinical outcome by decreasing the LDL cholesterol oxidation, hypercoagulability, oxidative stress and improving the level of endothelial nitric oxide synthesis in patients with type 2 diabetes and hypertension. However, the correlations between the ACEi and the serum markers for the vascular endothelial function in previous studies were not consistent. SUBJECTS AND METHODS: Between July 2003 and April 2005, 104 type 2 diabetes patients with hypertension, who had been admitted to 9 major university hospitals in Korea, were examined. The subjects were randomly allocated to the cilazapril (2.5~5 mg/day) and atenolol (50~100 mg/day) treatment group and given a combination of hydrochlorothiazide and amlodipine. The lipid profile and the markers for endothelial function, such as vWF, VCAM, E-selectin, tPA, fibrinogen, adiponectin, hsCRP, nitrotyrosine were evaluated and the differences in the variables were compared with those obtained 6 months later. RESULTS: A total 56 subjects completed the 6-months follow up period. Regarding the baseline characteristics, there were no significant differences in the variables observed in the two groups except for HbA1c (P = 0.037), vWF (P = 0.048), and hsCRP (P = 0.038). After 6 months, both groups showed a significant and identical decrease in the systolic and diastolic blood pressure compared with the baseline (P < 0.002). However, there were no significant differences in the endothelial markers between each group. On the other hand, there was some deterioration in the triglyceride (P = 0.009) and HbA1c (P = 0.017) levels in the atenolol treatment groups. CONCLUSIONS: There were no significant differences in the endothelial function markers observed between the cilazapril and atenolol groups. However, cilazapril had an identical effect on the blood pressure reduction compared with atenolol but had fewer adverse effects on the glucose and lipid metabolism.

Citations

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  • Potential Protective Role of Blood Pressure-Lowering Drugs on the Balance between Hemostasis and Fibrinolysis in Hypertensive Patients at Rest and During Exercise
    Annabella Braschi
    American Journal of Cardiovascular Drugs.2019; 19(2): 133.     CrossRef
Review
Disturbed Shear Stress Induces Inflammation and Atherosclerosis-Role of BMP4 as a Mechanosensitive and Inflammatory Cytokine.
Hanjoong Jo, Hannah Song
Korean Diabetes J. 2005;29(4):271-281.   Published online July 1, 2005
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AbstractAbstract PDF
Atherosclerosis is an inflammatory disease occurring preferentially in arterial regions exposed to disturbed flow conditions including oscillatory shear stress(OS). In contrast, the arterial regions exposed to laminar shear(LS) are relatively lesion-free. The opposite effects of LS(atheroprotective) and OS(atherogenic) are likely to be determined by differential expression of genes and proteins. Therefore, numerous investigators including us carried out transcript profiling studies to identify mechanosensitive genes that are turned on or off in response to different shear conditions. Through this and subsequent verification approaches using both cultured endothelial cells and human coronary arteries containing atherosclerotic lesions, we discovered that BMP4 expression is a highly regulated by different shear conditions. More importantly, we discovered a novel role of BMP4 as a mechanosensitive pro-inflammatory cytokine. Exposing endothelial cells to OS increased BMP4 protein expression while LS decreased it. Also, we found BMP4 expression only in the selective patches of endothelial cells overlying foam cell lesions in human coronary arteries. Chronic exposure of endothelial cells to OS stimulates inflammatory responses in endothelial cells such as production of intercellular adhesion molecule 1(ICAM-1) leading to monocyte adhesion to endothelium. A series of studies have revealed that exposure to OS induces inflammatory responses by producing BMP4 in endothelial cells. BMP4 then stimulates ICAM-1 expression and monocyte adhesion by the reactive oxygen species(ROS) and NF kappa B-dependent mechanisms. ROS produced in response to OS and BMP4 are derived from NADPH oxidase involving nox1 and p47phox components. These findings strongly suggest that BMP4 is a mechanosensitive, inflammatory factor playing a critical role in early steps of atherogenesis in atheroprone areas. This review is written to summarize this emerging field of shear stress, inflammation and atherosclerosis.
Original Article
An Effect of Estrogen Supplementation on the Endothelium Dependent Vasodilation in Postmenopausal Women with Type 2 Diabetes Mellitus.
Jun Kim Yeo, Sang Jun Lee, In Kyu Lee
Korean Diabetes J. 2000;24(1):37-45.   Published online January 1, 2001
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AbstractAbstract PDF
BACKGROUND
Although estrogen supplementation can reduce cardiovascular events in postmenopausal women, but the mechanism that mediate this beneficial effect is unclear. Thus, we investigated the acute effect of HRT on endothelial dependent vasodilation using high resolution ultrasound in healthy and diabetic postmenopausal women. METHOD: We examined endogenous (flow dependent dilatation affer 5min cuff occlusion) and exogenous (sublingual nitroglycerin) nitric oxide mediated vasodilation in the brachial artery before and after estrogen supplementation (Premarin R 0.625 mg for 1 wk) in 16 postmenopausal women, and in 18 age-matched postmenopausal women with type 2 diabetes mellitus. RESULTS: There were no differences in age, total & LDL cholesterol level, and body mass index between the groups (p>0.05). However, HDL cholesterol level was significantly lower in patient with diabetes than in normal women (1.0+/-0.3 mmol/L in diabetes and 1.4+/-0.2 mmol/L in normal, p<0.05). Basal endothelium dependent vascular reactivity was significantly attenuated in patient with diabetes when compaired with normal subjects (8.0+/-3,9% versus 13.7+/-6.2%, p<0.05). An estrogen supplementation increased endothelium dependent vasodilation not only in patient with diabetes(from 8.0+/-3.9% to 15.1+/-4.0%, p<0.05), but also in normal women (from 13.7+/-6.2% to 20.1+/-4.7%, p<0.05). Moreover the percent increase of vascular reactivity was higher in patient with diabetes(p<0,05), In contrast, the responses to sublingual nitroglycerin were comparable in diabetes (from 21.1+/-6.0% to 22.1+/-4.1%, p>0.05), and in normal women (from 25.8+/-7.8% to 25.2+/-4.5%, p>0.05) before and after estrogen supplementation. CONCLUSION: Endothelial dysfunction was prominent in patient with diabetes and it was significantly attenuated by estrogen. These results suggest that estrogen replacement improves endothelial dependent vasodilation in healthy and diabetic postmenopausal women.

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