Worse cardiac remodeling in response to pressure overload in type 2 diabetes mellitus☆
Section snippets
Background
Diabetes mellitus (DM) is a chronic metabolic disease that results from pancreas' inability to produce insulin, such as in Type 1 DM (T1DM), or from the incapacity of the organs to use insulin, as in Type 2 DM (T2DM). This impairment of insulin production and/or utilization and consequent hyperglycemia instigates multiple organ failure, including those of the cardiovascular system [1]. The incidence of diabetes mellitus has dramatically increased worldwide and in the next years the number of
Experimental animal model
This study was made according to the Guide for the Care and Use of Laboratory Animals published by the NIH (NIH Publication no. 85-23, revised 2011) and with the Portuguese law of animal welfare (DL 129/92, DL 197/96; P 1131/97). The Faculty of Medicine of the Universidade do Porto is a governmental institution granted with approval to perform animal experiments by the Portuguese Government.
Male Wistar Han rats were obtained from Charles River (Spain) and housed in groups of 5 per cage in a
Morphometric characterization
All animals with T1DM presented lower BW but increased heart, lung and renal indexed weight (Table 3). The simultaneous presence of pressure overload had no impact in the parameters mentioned before. The ingestion of a HCD for 5 weeks did not alter body weight of the DM2 animals, neither the weight of other organs analyzed. On the contrary, the DB2 group presented cardiac hypertrophy and evidences of lung congestion.
Cardiac structure
Echocardiographic results of both protocols are summarized in Fig. 1. The
Discussion
Since the recognition of diabetic cardiomyopathy in the 1970s [20], researchers have tried to unravel the mechanisms instigating this disease. However, the majority of the papers focus their attention in one type of DM and in one ventricle, neglecting the importance of the RV for myocardial function. In our study we used two well-known animal models of DM and compared the magnitude of the biventricular adaptations triggered either by T1DM or T2DM. Furthermore, since the prevalence of
Conclusion
In conclusion, our study demonstrates that both types of diabetes induce distinct cardiac alterations per se and when combined with chronic pressure overload. The T1DM promotes a more pronounced hypertrophy and extracellular matrix remodeling, whereas T2DM has higher impact in myocardial function, either in the LV as in the RV. The simultaneous presence of pressure overload had cardiac repercussions only in the DB2 group, impairing biventricular systolic and diastolic functions.
Funding
This work was supported by Portuguese Foundation for Science and Technology Grant UID/IC/00051/2013 financed with national funds by Fundação para a Ciência e Tecnologia and by Fundo Europeu de Desenvolvimento Regional through COMPETE 2020 – Programa Operacional Competitividade e Internacionalização (POCI), EXCL-II/BIM-MEC/0055/2012, and by European Commission Grant FP7-Health-2010, MEDIA-261409. This work was supported by Portuguese Foundation for Science and Technology Grant SFRH/BD/66628/2009
Competing and conflicting interests
The authors declare that they have no conflict of interests.
Author contribution
Nádia Gonçalves: conception and design of research; performed experiments; analyzed data; interpreted results of experiments; prepared figures; drafted manuscript, approved final version of manuscript.
Carla Gomes-Ferreira: performed experiments; analyzed data; prepared figures; drafted manuscript, approved final version of manuscript.
Cláudia Moura: performed experiments; analyzed data, approved final version of manuscript.
Roberto Roncon-Albuquerque Jr: conception and design of research;
Acknowledgments
The authors thank Ana Filipa Silva and Cláudia Mendes for the cardiac histological evaluation and Patrícia Gonçalves Rodrigues for isolated cardiomyocyte's analysis. The authors thank André Lourenço for the statistical analysis.
References (36)
- et al.
Diabetes-associated cardiac fibrosis: cellular effectors, molecular mechanisms and therapeutic opportunities
J. Mol. Cell. Cardiol.
(2016) - et al.
Uncomplicated type 1 diabetes and preclinical left ventricular myocardial dysfunction: insights from echocardiography and exercise cardiac performance evaluation
Diabetes Res. Clin. Pract.
(2008) - et al.
Alpha-lipoic acid attenuates cardiac fibrosis in Otsuka Long–Evans Tokushima Fatty rats
Cardiovasc. Diabetol.
(2012) - et al.
Adipocytokines in relation to cardiovascular disease
Metab. Clin. Exp.
(2013) - et al.
Diabetic cardiomyopathy: pathophysiology and clinical features
Heart Fail. Rev.
(2013) - et al.
ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD)
Eur. Heart J.
(2013) - et al.
Diabetic cardiomyopathy revisited
Circulation
(2007) - et al.
Markers of oxidative stress during diabetes mellitus
J. Biomark.
(2013) - et al.
Oxidative stress and myocardial injury in the diabetic heart
J. Pathol.
(2013) - et al.
Advanced glycation end product accumulation in the cardiomyocytes of heart failure patients with and without diabetes
Ann. Transplant.
(2012)
Diastolic stiffness of the failing diabetic heart: importance of fibrosis, advanced glycation end products, and myocyte resting tension
Circulation
Tissue advanced glycation end products are associated with diastolic function and aerobic exercise capacity in diabetic heart failure patients
Eur. J. Heart Fail.
Advanced glycation end product cross-linking: pathophysiologic role and therapeutic target in cardiovascular disease
Congest. Heart Fail.
A breaker of advanced glycation end products attenuates diabetes-induced myocardial structural changes
Circ. Res.
Effects of diabetes mellitus, pressure-overload and their association on myocardial structure and function
Am. J. Hypertens.
Diastolic dysfunction in patients with type 2 diabetes mellitus: is it really the first marker of diabetic cardiomyopathy?
J. Am. Soc. Echocardiogr.
Diabetic cardiomyopathy in Zucker diabetic fatty rats: the forgotten right ventricle
Cardiovasc. Diabetol.
Comorbidities of diabetes and hypertension: mechanisms and approach to target organ protection
J. Clin. Hypertens. (Greenwich)
Cited by (0)
- ☆
All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
- 1
These authors contributed equally to this work.