Angiotensin II type 1 receptor blocker attenuates diabetes-induced atrial structural remodeling

Kato, Takeshi; Yamashita, Takeshi; Sekiguchi, Akiko; Tsuneda, Takayuki; Sagara, Kouichi; Takamura, Masayuki; Kaneko, Shuichi; Aizawa, Tadanori; Fu, Long-Tai

doi:10.1016/j.jjcc.2011.06.003

Cited by 19 publications

(18 citation statements)

References 33 publications

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“…Candesartan significantly reduces expression of connective tissue growth factor and effectively suppresses the development of fibrotic deposition in diabetic rats [93]. Furthermore, candesartan reduces accumulation of AGEs and subsequent albuminuria by downregulating the nicotinamide adenine dinucleotide phosphate oxidase p47phox component and by inducing NO synthase expression, as well as by attenuating expression of RAGE in type 2 diabetic KK/Ta mouse kidneys [94].…”

Section: Hmgb1/rage and Risk Factors Of Strokementioning

confidence: 99%

Potential of the Angiotensin Receptor Blockers (ARBs) Telmisartan, Irbesartan, and Candesartan for Inhibiting the HMGB1/RAGE Axis in Prevention and Acute Treatment of Stroke

Kikuchi

Tancharoen

Ito

et al. 2013

IJMS

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Stroke is a major cause of mortality and disability worldwide. The main cause of stroke is atherosclerosis, and the most common risk factor for atherosclerosis is hypertension. Therefore, antihypertensive treatments are recommended for the prevention of stroke. Three angiotensin receptor blockers (ARBs), telmisartan, irbesartan and candesartan, inhibit the expression of the receptor for advanced glycation end-products (RAGE), which is one of the pleiotropic effects of these drugs. High mobility group box 1 (HMGB1) is the ligand of RAGE, and has been recently identified as a lethal mediator of severe sepsis. HMGB1 is an intracellular protein, which acts as an inflammatory cytokine when released into the extracellular milieu. Extracellular HMGB1 causes multiple organ failure and contributes to the pathogenesis of hypertension, hyperlipidemia, diabetes mellitus, atherosclerosis, thrombosis, and stroke. This is the first review of the literature evaluating the potential of three ARBs for the HMGB1-RAGE axis on stroke therapy, including prevention and acute treatment. This review covers clinical and experimental studies conducted between 1976 and 2013. We propose that ARBs, which inhibit the HMGB1/RAGE axis, may offer a novel option for prevention and acute treatment of stroke. However, additional clinical studies are necessary to verify the efficacy of ARBs.

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Section: Hmgb1/rage and Risk Factors Of Strokementioning

confidence: 99%

Potential of the Angiotensin Receptor Blockers (ARBs) Telmisartan, Irbesartan, and Candesartan for Inhibiting the HMGB1/RAGE Axis in Prevention and Acute Treatment of Stroke

Kikuchi

Tancharoen

Ito

et al. 2013

IJMS

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“…Several studies indicate that RAA inhibition suppresses the expression of RAGE and connective tissue growth factor (CTGF) as well as AGE formation [68][69][70][71][72]. In streptozotocin-induced diabetic rats Kato et al demonstrated that treatment with candesartan reduces CTGF expression and effectively suppresses the development of atrial fibrotic deposition [73]. The attenuation of CTGF expression by candesartan may be derived via decreased AGE interaction with RAGE and/or from a direct effect of the drug [73].…”

Section: Upstream Therapies For Diabetes Mellitus Related Atrial Remomentioning

confidence: 99%

Diabetes mellitus and atrial fibrillation: Pathophysiological mechanisms and potential upstream therapies

Goudis¹,

Korantzopoulos

Ntalas

et al. 2015

International Journal of Cardiology

115

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“…Early studies identified Ang II and its signaling effectors as potential culprits for triggering LV hypertrophy (LVH), fibrosis and cardiac remodeling; but many studies are now supporting at least a synergistic role for aldosterone in the pathogenesis of cardiac fibrosis observed as a result of the diabetes-induced metabolic impairment (19,26,41,55,70,97,106). These observations are also supported by the fact that the serum levels of aldosterone have been found to be increased in the pre-diabetic and diabetic conditions and contribute to the LVH and cardiac fibrosis seen in these conditions (26,106).…”

Section: Development and Progression Of Cardiac Dysfunction As A Resumentioning

confidence: 99%

Molecular and metabolic mechanisms of cardiac dysfunction in diabetes

et al. 2013

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Diabetes mellitus type 2 (T2DM) is a widespread chronic medical condition with prevalence bordering on the verge of an epidemic. It is of great concern that cardiovascular disease is more common in patients with diabetes than the non-diabetic population. While hypertensive and ischemic heart disease is more common in diabetic patients, there is another type of heart disease in diabetes that is not associated with hypertension or coronary artery disease. This muscle functional disorder is termed “diabetic cardiomyopathy”. Diastolic dysfunction characterized by impaired diastolic relaxation time and reduced contractility precedes systolic dysfunction and is the main pathogenic hallmark of this condition. Even though the pathogenesis of “diabetic cardiomyopathy” is still controversial, impaired cardiac insulin sensitivity and metabolic overload are emerging as major molecular and metabolic mechanisms for cardiac dysfunction. Systemic insulin resistance, hyperinsulinemia, dysregulation of adipokine secretion, increases in circulating levels of inflammatory mediators, aberrant activation of renin angiotensin aldosterone system (RAAS), and increased oxidative stress contribute dysregulated insulin and metabolic signaling in the heart and development of diastolic dysfunction. In addition, maladaptive calcium homeostasis and endothelial cell dysregulation endoplasmic reticular stress play a potential role in cardiomyocyte fibrosis/diastolic dysfunction. In this review, we will focus on emerging molecular and metabolic pathways underlying cardiac dysfunction in diabetes. Elucidation of these mechanisms should provide a better understanding of the various cardiac abnormalities associated with diastolic dysfunction and its progression to systolic dysfunction and heart failure.

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Angiotensin II type 1 receptor blocker attenuates diabetes-induced atrial structural remodeling

Abstract: Candesartan reduced CTGF expression and attenuated the fibrosis in diabetic rat atria. These results implied the protective effects of candesartan on diabetes-related atrial arrhythmias.

Cited by 19 publications

References 33 publications

Potential of the Angiotensin Receptor Blockers (ARBs) Telmisartan, Irbesartan, and Candesartan for Inhibiting the HMGB1/RAGE Axis in Prevention and Acute Treatment of Stroke

Potential of the Angiotensin Receptor Blockers (ARBs) Telmisartan, Irbesartan, and Candesartan for Inhibiting the HMGB1/RAGE Axis in Prevention and Acute Treatment of Stroke

Diabetes mellitus and atrial fibrillation: Pathophysiological mechanisms and potential upstream therapies

Molecular and metabolic mechanisms of cardiac dysfunction in diabetes

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