Mechanisms of endothelial dysfunction in obesity-associated hypertension

Abstract

Obesity is strongly associated with high blood pressure, dyslipidemia, and type 2 diabetes. These conditions synergistically increase the risk of cardiovascular events. A number of central and peripheral abnormalities can explain the development or maintenance of high blood pressure in obesity. Of great interest is endothelial dysfunction, considered to be a primary risk factor in the development of hypertension. Additional mechanisms also related to endothelial dysfunction have been proposed to mediate the development of hypertension in obese individuals. These include: increase in both peripheral vasoconstriction and renal tubular sodium reabsorption, increased sympathetic activity and overactivation of both the renin-angiotensin system and the endocannabinoid system and insulin resistance. The discovery of new mechanisms regulating metabolic and vascular function and a better understanding of how vascular function can be influenced by these systems would facilitate the development of new therapies for treatment of obesity-associated hypertension.

Tetrahydroxystilbene Glycoside Improves Microvascular Endothelial Dysfunction and Ameliorates Obesity-Associated Hypertension in Obese ZDF Rats Via Inhibition of Endothelial Autophagy

“…According to the Global Burden of Disease Study [2], between 1980 and 2013 worldwide the proportion of men who were overweight or obese increased from 28.8% to 36.9%, and the respective proportion of women increased from 29.8% to 38.0%. Obese patients have a six-fold increased risk of hypertension compared with people of average size [3]. Despite these alarming statistics, the molecular mechanisms underlying the obesity-associated increase in arterial blood pressure (BP) are not known, and the number of effective drug interventions is limited.…”

Relationship of Metabolic Parameters and Vascular Remodelling in Comorbidity of Essential Hypertension, Type 2 Diabetes and Obesity

“…Критерiями включення в дослiдження були: ГХ II ста-дiї, 2 ступеня; ЦД 2 типу середньої важ-костi, субкомпенсований; хронiчна серцева недостатнiсть (ХСН) 0-II функцiонального класу (ФК); нормальна маса тiла (iндекс маси тiла (IМТ) 18-24,9), надмiрна вага 9), ожирiння (Ож) I ступе-ня 9); абдомiнальне ожирiн-ня; нормальна швидкiсть клубочкової фiль-трацiї (ШКФ); нормокреатинiнемiя; вiдсут-нiсть протеїнурiї (допустима лише мiкроаль-бумiнурiя); фракцiя викиду > 50 %; вiк па-цiєнтiв 45-60 рокiв; встановлена тривалiсть захворювання ГХ 8-12 рокiв, ЦД 2 ти-пу 3-7 рокiв; нерегулярний прийом ан-тигiпертензивних препаратiв. Критерiями виключення iз дослiдження були: наявнiсть супутньої патологiї у пацiєнтiв з ГХ i ЦД 2 типу, ЦД 1 типу; ГХ III стадiї, 3 ступеню; ХСН III-IV ФК; ЦД 2 типу у легкiй i важкiй формах, фазах компенсацiї та декомпенса-цiї; iнсулiнотерапiя у пацiєнтiв з ЦД 2 типу; Ож II-III ступенiв; знижена ШКФ; наяв-нiсть протеїнурiї; ФВ < 50 %; вiк пацiєнтiв менше 45 та бiльше 60 рокiв; ехонегатив-нiсть; вiдмова пацiєнтiв вiд дослiдження.…”

“…Метаболiчнi детермiнанти ЦД 2 типу потенцiйно здатнi запускати пaтофiзiоло-гiчний каскад, що приводить до ендотелiаль-ної дисфункцiї (ЕД), ремоделювання серця i судин, активацiї iмунозaпальних процесiв та апоптозу [9,10].…”

Coexistence of endothelial dysfunction, fibrinolysis activation and diminished interleukin 6 level in morbid obesity

“…Other health conditions such as insulin resistance and diabetes cause associated medical complications in obese patients [3,4,5,6].…”

“…Mechanical damage or loss of endothelial integrity elicits endothelial activation and brings about pathological disorders such as hypertension, atherosclerotic lesion or thrombus formation [3]. Vascular dysfunction is associated with insufficient or excessive production of specific markers of endothelial damage, such as von Willebrand factor (vWF) or soluble thrombomodulin (sTM) [6,7,8], and other parameters of fibrinolysis, such as tissue plasminogen activator (t-PA) and plasminogen activator of inhibitor type 1 antigen (PAI-1:Ag) [4,9,10,11].…”