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Targeting the upregulation of reactive oxygen species subsequent to hyperglycemia prevents type 1 diabetic cardiomyopathy in mice.
Free Radic Biol Med 2013; 60:307-17FR

Abstract

Cardiac oxidative stress is an early event associated with diabetic cardiomyopathy, triggered by hyperglycemia. We tested the hypothesis that targeting left-ventricular (LV) reactive oxygen species (ROS) upregulation subsequent to hyperglycemia attenuates type 1 diabetes-induced LV remodeling and dysfunction, accompanied by attenuated proinflammatory markers and cardiomyocyte apoptosis. Male 6-week-old mice received either streptozotocin (55mg/kg/day for 5 days), to induce type 1 diabetes, or citrate buffer vehicle. After 4 weeks of hyperglycemia, the mice were allocated to coenzyme Q10 supplementation (10mg/kg/day), treatment with the angiotensin-converting-enzyme inhibitor (ACE-I) ramipril (3mg/kg/day), treatment with olive oil vehicle, or no treatment for 8 weeks. Type 1 diabetes upregulated LV NADPH oxidase (Nox2, p22(phox), p47(phox) and superoxide production), LV uncoupling protein UCP3 expression, and both LV and systemic oxidative stress (LV 3-nitrotyrosine and plasma lipid peroxidation). All of these were significantly attenuated by coenzyme Q10. Coenzyme Q10 substantially limited type 1 diabetes-induced impairments in LV diastolic function (E:A ratio and deceleration time by echocardiography, LV end-diastolic pressure, and LV -dP/dt by micromanometry), LV remodeling (cardiomyocyte hypertrophy, cardiac fibrosis, apoptosis), and LV expression of proinflammatory mediators (tumor necrosis factor-α, with a similar trend for interleukin IL-1β). Coenzyme Q10's actions were independent of glycemic control, body mass, and blood pressure. Coenzyme Q10 compared favorably to improvements observed with ramipril. In summary, these data suggest that coenzyme Q10 effectively targets LV ROS upregulation to limit type 1 diabetic cardiomyopathy. Coenzyme Q10 supplementation may thus represent an effective alternative to ACE-Is for the treatment of cardiac complications in type 1 diabetic patients.

Authors+Show Affiliations

Baker IDI Heart and Diabetes Institute, Melbourne 8008, VIC, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23454064

Citation

Huynh, Karina, et al. "Targeting the Upregulation of Reactive Oxygen Species Subsequent to Hyperglycemia Prevents Type 1 Diabetic Cardiomyopathy in Mice." Free Radical Biology & Medicine, vol. 60, 2013, pp. 307-17.
Huynh K, Kiriazis H, Du XJ, et al. Targeting the upregulation of reactive oxygen species subsequent to hyperglycemia prevents type 1 diabetic cardiomyopathy in mice. Free Radic Biol Med. 2013;60:307-17.
Huynh, K., Kiriazis, H., Du, X. J., Love, J. E., Gray, S. P., Jandeleit-Dahm, K. A., ... Ritchie, R. H. (2013). Targeting the upregulation of reactive oxygen species subsequent to hyperglycemia prevents type 1 diabetic cardiomyopathy in mice. Free Radical Biology & Medicine, 60, pp. 307-17. doi:10.1016/j.freeradbiomed.2013.02.021.
Huynh K, et al. Targeting the Upregulation of Reactive Oxygen Species Subsequent to Hyperglycemia Prevents Type 1 Diabetic Cardiomyopathy in Mice. Free Radic Biol Med. 2013;60:307-17. PubMed PMID: 23454064.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Targeting the upregulation of reactive oxygen species subsequent to hyperglycemia prevents type 1 diabetic cardiomyopathy in mice. AU - Huynh,Karina, AU - Kiriazis,Helen, AU - Du,Xiao-Jun, AU - Love,Jane E, AU - Gray,Stephen P, AU - Jandeleit-Dahm,Karin A, AU - McMullen,Julie R, AU - Ritchie,Rebecca H, Y1 - 2013/02/26/ PY - 2012/12/23/received PY - 2013/02/05/revised PY - 2013/02/21/accepted PY - 2013/3/5/entrez PY - 2013/3/5/pubmed PY - 2013/11/2/medline SP - 307 EP - 17 JF - Free radical biology & medicine JO - Free Radic. Biol. Med. VL - 60 N2 - Cardiac oxidative stress is an early event associated with diabetic cardiomyopathy, triggered by hyperglycemia. We tested the hypothesis that targeting left-ventricular (LV) reactive oxygen species (ROS) upregulation subsequent to hyperglycemia attenuates type 1 diabetes-induced LV remodeling and dysfunction, accompanied by attenuated proinflammatory markers and cardiomyocyte apoptosis. Male 6-week-old mice received either streptozotocin (55mg/kg/day for 5 days), to induce type 1 diabetes, or citrate buffer vehicle. After 4 weeks of hyperglycemia, the mice were allocated to coenzyme Q10 supplementation (10mg/kg/day), treatment with the angiotensin-converting-enzyme inhibitor (ACE-I) ramipril (3mg/kg/day), treatment with olive oil vehicle, or no treatment for 8 weeks. Type 1 diabetes upregulated LV NADPH oxidase (Nox2, p22(phox), p47(phox) and superoxide production), LV uncoupling protein UCP3 expression, and both LV and systemic oxidative stress (LV 3-nitrotyrosine and plasma lipid peroxidation). All of these were significantly attenuated by coenzyme Q10. Coenzyme Q10 substantially limited type 1 diabetes-induced impairments in LV diastolic function (E:A ratio and deceleration time by echocardiography, LV end-diastolic pressure, and LV -dP/dt by micromanometry), LV remodeling (cardiomyocyte hypertrophy, cardiac fibrosis, apoptosis), and LV expression of proinflammatory mediators (tumor necrosis factor-α, with a similar trend for interleukin IL-1β). Coenzyme Q10's actions were independent of glycemic control, body mass, and blood pressure. Coenzyme Q10 compared favorably to improvements observed with ramipril. In summary, these data suggest that coenzyme Q10 effectively targets LV ROS upregulation to limit type 1 diabetic cardiomyopathy. Coenzyme Q10 supplementation may thus represent an effective alternative to ACE-Is for the treatment of cardiac complications in type 1 diabetic patients. SN - 1873-4596 UR - https://www.unboundmedicine.com/medline/citation/23454064/Targeting_the_upregulation_of_reactive_oxygen_species_subsequent_to_hyperglycemia_prevents_type_1_diabetic_cardiomyopathy_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891-5849(13)00074-9 DB - PRIME DP - Unbound Medicine ER -