Journal article
Authors list: Koncsos, Gabor; Varga, Zoltan V.; Baranyai, Tamas; Boengler, Kerstin; Rohrbach, Susanne; Li, Ling; Schlueter, Klaus-Dieter; Schreckenberg, Rolf; Radovits, Tamas; Olah, Attila; Matyas, Csaba; Lux, Arpad; Al-Khrasani, Mahmoud; Komlodi, Timea; Bukosza, Nora; Mathe, Domokos; Deres, Laszlo; Bartekova, Monika; Rajtik, Tomas; Adameova, Adriana; Szigeti, Krisztian; Hamar, Peter; Helyes, Zsuzsanna; Tretter, Laszlo; Pacher, Pal; Merkely, Bela; Giricz, Zoltan; Schulz, Rainer; Ferdinandy, Peter
Publication year: 2016
Pages: H927-H943
Journal: American Journal of Physiology - Heart and Circulatory Physiology
Volume number: 311
Issue number: 4
ISSN: 0363-6135
eISSN: 1522-1539
Open access status: Green
DOI Link: https://doi.org/10.1152/ajpheart.00049.2016
Publisher: American Physiological Society
Abstract:
Although incidence and prevalence of prediabetes are increasing, little is known about its cardiac effects. Therefore, our aim was to investigate the effect of prediabetes on cardiac function and to characterize parameters and pathways associated with deteriorated cardiac performance. Long-Evans rats were fed with either control or high-fat chow for 21 wk and treated with a single low dose (20 mg/kg) of streptozotocin at week 4. High-fat and streptozotocin treatment induced prediabetes as characterized by slightly elevated fasting blood glucose, impaired glucose and insulin tolerance, increased visceral adipose tissue and plasma leptin levels, as well as sensory neuropathy. In prediabetic animals, a mild diastolic dysfunction was observed, the number of myocardial lipid droplets increased, and left ventricular mass and wall thickness were elevated; however, no molecular sign of fibrosis or cardiac hypertrophy was shown. In prediabetes, production of reactive oxygen species was elevated in subsarcolemmal mitochondria. Expression of mitofusin-2 was increased, while the phosphorylation of phos-pholamban and expression of Bcl-2/adenovirus E1B 19-kDa protein-interacting protein 3 (BNIP3, a marker of mitophagy) decreased. However, expression of other markers of cardiac auto-and mitophagy, mitochondrial dynamics, inflammation, heat shock proteins, Ca2+/calmodulin-dependent protein kinase II, mammalian target of rapamycin, or apoptotic pathways were unchanged in prediabetes. This is the first comprehensive analysis of cardiac effects of prediabetes indicating that mild diastolic dysfunction and cardiac hypertrophy are multifactorial phenomena that are associated with early changes in mitophagy, cardiac lipid accumulation, and elevated oxidative stress and that prediabetes-induced oxidative stress originates from the subsarcolemmal mitochondria.
Citation Styles
Harvard Citation style: Koncsos, G., Varga, Z., Baranyai, T., Boengler, K., Rohrbach, S., Li, L., et al. (2016) Diastolic dysfunction in prediabetic male rats: Role of mitochondrial oxidative stress, American Journal of Physiology - Heart and Circulatory Physiology, 311(4), pp. H927-H943. https://doi.org/10.1152/ajpheart.00049.2016
APA Citation style: Koncsos, G., Varga, Z., Baranyai, T., Boengler, K., Rohrbach, S., Li, L., Schlueter, K., Schreckenberg, R., Radovits, T., Olah, A., Matyas, C., Lux, A., Al-Khrasani, M., Komlodi, T., Bukosza, N., Mathe, D., Deres, L., Bartekova, M., Rajtik, T., ...Ferdinandy, P. (2016). Diastolic dysfunction in prediabetic male rats: Role of mitochondrial oxidative stress. American Journal of Physiology - Heart and Circulatory Physiology. 311(4), H927-H943. https://doi.org/10.1152/ajpheart.00049.2016
Keywords
ANIMAL-MODELS; CARDIOVASCULAR-DISEASE; CONTRACTILE DYSFUNCTION; DIABETES-MELLITUS; diabetic cardiomyopathy; IMPAIRED FASTING GLUCOSE; INDUCED CARDIAC-HYPERTROPHY; LEFT-VENTRICULAR HYPERTROPHY; OXIDASE 4 NOX4
