Oxidative Stress and Cardiomyocyte Necrosis With Elevated Serum Troponins: Pathophysiologic Mechanisms

Robinson, Arthur L.; Newman, Kevin P.; Weber, Karl T.; Ramanathan, Kodangudi B.; McGee, Jesse E.

doi:10.1097/maj.0b013e3182231ee3

Cited by 19 publications

(16 citation statements)

References 99 publications

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“…Our findings, when considered together with previous literature data, suggest that the bidirectional PTH–CVD relationships may form a vicious circle in which the interaction between PTH and RAAS plays an important role 146,147,190. It has been hypothesized that in patients with CVD (especially with hypertension and chronic heart failure) inappropriate activation of the RAAS and salt retention causes marked losses of cations (calcium, magnesium) with a consequent increase of PTH production, which in turn stimulates RAAS.…”

Section: Discussionsupporting

confidence: 81%

Cardiovascular diseases in older patients with osteoporotic hip fracture: prevalence, disturbances in mineral and bone metabolism, and bidirectional links

Fisher¹,

Srikusalanukul²,

Davis³

et al. 2013

CIA

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BackgroundConsiderable controversy exists regarding the contribution of mineral/bone metabolism abnormalities to the association between cardiovascular diseases (CVDs) and osteoporotic fractures.Aims and methodsTo determine the relationships between mineral/bone metabolism biomarkers and CVD in 746 older patients with hip fracture, clinical data were recorded and serum concentrations of parathyroid hormone (PTH), 25-hydroxyvitamin D, calcium, phosphate, magnesium, troponin I, parameters of bone turnover, and renal, liver, and thyroid functions were measured.ResultsCVDs were diagnosed in 472 (63.3%) patients. Vitamin D deficiency was similarly prevalent in patients with (78.0%) and without (82.1%) CVD. The CVD group had significantly higher mean PTH concentrations (7.6 vs 6.0 pmol/L, P < 0.001), a higher prevalence of secondary hyperparathyroidism (SPTH) (PTH > 6.8 pmol/L, 43.0% vs 23.3%, P < 0.001), and excess bone resorption (urinary deoxypyridinoline corrected by creatinine [DPD/Cr] > 7.5 nmol/μmol, 87.9% vs 74.8%, P < 0.001). In multivariate regression analysis, SHPT (odds ratio [OR] 2.6, P = 0.007) and high DPD/Cr (OR 2.8, P = 0.016) were independent indictors of CVD. Compared to those with both PTH and DPD/Cr in the normal range, multivariate-adjusted ORs for the presence of CVD were 17.3 (P = 0.004) in subjects with SHPT and 9.7 (P < 0.001) in patients with high DPD/Cr. CVD was an independent predicator of SHPT (OR 2.8, P = 0.007) and excess DPD/Cr (OR 2.5, P = 0.031). CVD was predictive of postoperative myocardial injury, while SHPT was also an independent predictor of prolonged hospital stay and in-hospital death.ConclusionSHPT and excess bone resorption are independent pathophysiological mediators underlying the bidirectional associations between CVD and hip fracture, and therefore are important diagnostic and therapeutic targets.

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Section: Discussionsupporting

confidence: 81%

Cardiovascular diseases in older patients with osteoporotic hip fracture: prevalence, disturbances in mineral and bone metabolism, and bidirectional links

Fisher¹,

Srikusalanukul²,

Davis³

et al. 2013

CIA

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“…More importantly, the elimination of the protective effect in AC5 KO × MnSOD +/− mice is direct evidence that indicates the importance of MnSOD in the AC5 regulatory pathway. Other studies have found that oxidative stress is an important mechanism mediating several different cardiomyopathies, 28–30, 33, 34 and Dai et al, showed the importance of mitochondrial oxidative stress. 35 However, the signaling pathways have not been elucidated.…”

Section: Discussionmentioning

confidence: 94%

Type 5 Adenylyl Cyclase Increases Oxidative Stress by Transcriptional Regulation of Manganese Superoxide Dismutase via the SIRT1/FoxO3a Pathway

et al. 2013

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Background For reasons that remain unclear, whether type 5 AC (AC5), one of two major AC isoforms in heart, is protective or deleterious in response to cardiac stress is controversial. To reconcile this controversy we examined the cardiomyopathy induced by chronic isoproterenol (ISO) in AC5 transgenic (Tg) mice and the signaling mechanisms involved. Methods and Results Chronic ISO increased oxidative stress and induced more severe cardiomyopathy in AC5 Tg, as left ventricular (LV) ejection fraction fell 1.9 fold more than wild type (WT), along with greater LV dilation and increased fibrosis, apoptosis and hypertrophy. Oxidative stress induced by chronic ISO, detected by 8-OhDG was 15% greater, p=0.007, in AC5 Tg hearts, while protein expression of MnSOD was reduced by 38%, indicating that the susceptibility of AC5 Tg to cardiomyopathy may be due to decreased MnSOD expression. Consistent with this, susceptibility of the AC5 Tg to cardiomyopathy was suppressed by overexpression of MnSOD, whereas protection afforded by the AC5 KO was lost in AC5 KO×MnSOD+/− mice. Elevation of MnSOD was eliminated by both sirtuin and MEK inhibitors, suggesting both the SIRT1/FoxO3a and MEK/ERK pathway are involved in MnSOD regulation by AC5. Conclusion Overexpression of AC5 exacerbates the cardiomyopathy induced by chronic catecholamine stress by altering regulation of SIRT1/FoxO3a, MEK/ERK and MnSOD, resulting in oxidative stress intolerance, thereby shedding light on new approaches for treatment of heart failure.

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“…First, the production of superoxide may be high enough to overwhelm normal defenses. Catecholamine overstimulation increases mitochondrial ROS production due to signaling through protein kinase A (169) or Ca 2+ (170). Secondly, normal defenses comprising glutathione and glutathione S-transferase P (GSTP) may be attenuated.…”

Section: Reactive Oxygen Speciesmentioning

confidence: 99%

Mitochondrial remodeling: Rearranging, recycling, and reprogramming

Gottlieb¹,

Bernstein

2016

Cell Calcium

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Oxidative Stress and Cardiomyocyte Necrosis With Elevated Serum Troponins: Pathophysiologic Mechanisms

Cited by 19 publications

References 99 publications

Cardiovascular diseases in older patients with osteoporotic hip fracture: prevalence, disturbances in mineral and bone metabolism, and bidirectional links

Cardiovascular diseases in older patients with osteoporotic hip fracture: prevalence, disturbances in mineral and bone metabolism, and bidirectional links

Type 5 Adenylyl Cyclase Increases Oxidative Stress by Transcriptional Regulation of Manganese Superoxide Dismutase via the SIRT1/FoxO3a Pathway

Mitochondrial remodeling: Rearranging, recycling, and reprogramming

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