Evidence for a Causal Role of Oxidative Stress in the Myocardial Complications of Insulin Resistance

Ritchie, Rebecca H

doi:10.1016/j.hlc.2008.11.003

Cited by 46 publications

(35 citation statements)

References 99 publications

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“…Insulin resistance is an antecedent of type 2 diabetes, and both scenarios are associated with cardiac upregulation of reactive oxygen species (ROS) generation and systemic oxidative stress (17,33,35,39,42). Given that superoxide is a key trigger of both cardiomyocyte hypertrophy (24,40,41) and impaired vasoreactivity (9), its upregulation is widely regarded as a contributing factor to cardiovascular abnormalities in insulin resistance (9,12,22,34,39). In the present study, impaired systemic glucose tolerance and hyperinsulinemia were already evident at 12 wk of age in LCR rats, relative to their HCR counterparts (Table 1 and Fig.…”

Section: Discussionmentioning

confidence: 99%

“…This evidence, like that for cardiac remodeling, has largely been obtained in older animals (20 -30 wk of age) and whether LV dysfunction is impaired in younger animals remains to be determined. Often, changes at the level of LV diastolic function are more marked than systolic parameters (6,15), suggesting that LCR, like other models of metabolic syndrome and type 2 diabetes, may predispose to earlier onset of abnormalities in myocardial relaxation rather than contractile dysfunction (39). If permitted to proceed to senescence (Ն2 yr of age), marked dysfunction in both systolic and diastolic function are evident (21).…”

Section: A: LVmentioning

confidence: 99%

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Low intrinsic exercise capacity in rats predisposes to age-dependent cardiac remodeling independent of macrovascular function

Ritchie

Leo

Qin

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Woodman OL. Low intrinsic exercise capacity in rats predisposes to age-dependent cardiac remodeling independent of macrovascular function. Am J Physiol Heart Circ Physiol 304: H729 -H739, 2013. First published December 21, 2012; doi:10.1152/ajpheart.00638.2012.-Rats selectively bred for low (LCR) or high (HCR) intrinsic running capacity simultaneously present with contrasting risk factors for cardiovascular and metabolic disease. However, the impact of these phenotypes on left ventricular (LV) morphology and microvascular function, and their progression with aging, remains unresolved. We tested the hypothesis that the LCR phenotype induces progressive age-dependent LV remodeling and impairments in microvascular function, glucose utilization, and ␤-adrenergic responsiveness, compared with HCR. Hearts and vessels isolated from female LCR (n ϭ 22) or HCR (n ϭ 26) were studied at 12 and 35 wk. Nonselected N:NIH founder rats (11 wk) were also investigated (n ϭ 12). LCR had impaired glucose tolerance and elevated plasma insulin (but not glucose) and body-mass at 12 wk compared with HCR, with early LV remodeling. By 35 wk, LV prohypertrophic and glucose transporter GLUT4 gene expression were up-and downregulated, respectively. No differences in LV ␤-adrenoceptor expression or cAMP content between phenotypes were observed. Macrovascular endothelial function was predominantly nitric oxide (NO)-mediated in both phenotypes and remained intact in LCR for both age-groups. In contrast, mesenteric arteries microvascular endothelial function, which was impaired in LCR rats regardless of age. At 35 wk, endothelial-derived hyperpolarizing factor-mediated relaxation was impaired whereas the NO contribution to relaxation is intact. Furthermore, there was reduced ␤2-adrenoceptor responsiveness in both aorta and mesenteric LCR arteries. In conclusion, diminished intrinsic exercise capacity impairs systemic glucose tolerance and is accompanied by progressive development of LV remodeling. Impaired microvascular perfusion is a likely contributing factor to the cardiac phenotype. cardiomyocyte hypertrophy; cardiac fibrosis; insulin resistance; EDHF; low-capacity runner; metabolic syndrome; resistance arteries THE METABOLIC SYNDROME is a polygenic disorder that includes obesity, insulin resistance, type 2 diabetes, dyslipidemia, hypertension, and impaired glycemic control. The prevalence of this disorder is dramatically increasing and is strongly linked to cardiovascular diseases (23). The presence of cardiovascular risk factors that constitute the metabolic syndrome is correlated with impairments in aerobic capacity and vascular endothelial function, as well as increased heart failure risk, all of which are strong independent predictors of mortality (13,30,37,48). Furthermore, the myocardial and vascular abnormalities associated with the metabolic syndrome in general, and the associated impairments in insulin signaling, likely include alterations in myocardial structure (through cardiomyocyte hypertrophy, cardiac fibrosis, and/or impairm...

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Section: Discussionmentioning

confidence: 99%

Section: A: LVmentioning

confidence: 99%

Low intrinsic exercise capacity in rats predisposes to age-dependent cardiac remodeling independent of macrovascular function

Ritchie

Leo

Qin

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Cellular defense against free radical injury is mediated by several potent antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase, all of which physiologically reduce ROS levels (Burdon 1995;Ritchie 2009 (Sattler et al 1999;Dernbach et al 2004). However, in pathological conditions, like ischemic/reperfusion injury, when ROS are generated in excess or when the cellular antioxidant defense system is defective, ROS may interact degeneratively with cellular components, including proteins, lipids and nucleic acids, causing cellular dysfunction and even death (Dhalla et al 2000;Psotová et al 2004;Makazan et al 2007).…”

Section: Discussionmentioning

confidence: 99%

The protective effect of Ganoderma atrum polysaccharide against anoxia/reoxygenation injury in neonatal rat cardiomyocytes

Li¹,

Nie²,

Yan³

et al. 2009

Life Sciences

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“…Уровень ТГ положительно коррелирует с ИМТ и массой ЛЖ и отрицательно с его систолической функцией. За последние годы проведен ряд исследований, дока-зывающих возможность и механизмы липотоксиче-ского поражения миокарда при ожирении, при кото-ром изменяется как структура миокарда, так и его функциональное состояние [15,16].…”

Section: нейрогуморальные механизмы развитияunclassified

The Mechanisms of Heart Failure Development in Obesity

et al. 2018

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Evidence for a Causal Role of Oxidative Stress in the Myocardial Complications of Insulin Resistance

Cited by 46 publications

References 99 publications

Low intrinsic exercise capacity in rats predisposes to age-dependent cardiac remodeling independent of macrovascular function

Low intrinsic exercise capacity in rats predisposes to age-dependent cardiac remodeling independent of macrovascular function

The protective effect of Ganoderma atrum polysaccharide against anoxia/reoxygenation injury in neonatal rat cardiomyocytes

The Mechanisms of Heart Failure Development in Obesity

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