RGD Reference Report - Myocardial fibrosis and apoptosis, but not inflammation, are present in long-term experimental diabetes. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Myocardial fibrosis and apoptosis, but not inflammation, are present in long-term experimental diabetes.

Authors: Ares-Carrasco, S  Picatoste, B  Benito-Martin, A  Zubiri, I  Sanz, AB  Sanchez-Mino, MD  Ortiz, A  Egido, J  Tunon, J  Lorenzo, O 
Citation: Ares-Carrasco S, etal., Am J Physiol Heart Circ Physiol. 2009 Oct 9.
RGD ID: 2314021
Pubmed: PMID:19820199   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpheart.00157.2009   (Journal Full-text)

Aim: To study the myocardial damage secondary to long-term streptozotocin-induced type-1 Diabetes Mellitus (DM1). Methods: Normotensive and spontaneously hypertensive (SHR) rats received either streptozotocin injections or vehicle. After 22 or 6 weeks, DM1, SHR, DM1/SHR and control rats were sacrificed and the left ventricles studied by histology, Quantitative-PCR, Western Blot, ELISA and Electro-mobility Shift Assay. Cardiomyocyte cultures were also performed. Results: The expression of pro-fibrotic factors Transforming Growth Factor-beta (TGFbeta1), Connective tissue growth factor (CTGF) and matrix proteins was increased and the TGFbeta1-linked transcription factors p-Smad3/4 and AP-1 were activated in the DM1 myocardium. Pro-apoptotic molecules FasL, Fas, Bax and cleaved caspase-3 were also augmented. Myocardial injury in long-term hypertension shared these features. In addition, hypertension was associated with activation of NFkappaB, increased inflammatory cell infiltrate and expression of the mediators [interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNFalpha), monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), angiotensinogen and oxidants], which were absent in long-term DM1. At this stage, the combination of DM1 and hypertension resulted in non-significant additive effects. Moreover, the coexistence of DM1 blunted the inflammatory response to hypertension. Anti-inflammatory IL-10 and anti-oxidants were induced in long-term DM1 and DM1/SHR hearts. Myocardial inflammation was however observed in the short-term model. In cultured cardiomyocytes, IL-10, TGFbeta1 and catalase blocked the glucose-stimulated expression of pro-inflammatory genes. Conclusions: Fibrosis and apoptosis are features of long-term myocardial damage in experimental DM1. Associated hypertension does not induce additional changes. Myocardial inflammation is present in hypertension and short-term DM1, but is not a key feature in long-term DM1. Local reduction of pro-inflammatory factors and expression of anti-inflammatory and anti-oxidant molecules may underlie this effect. Key words: diabetes, hypertension, inflammation, heart.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Diabetes Mellitus  ISOCcn2 (Rattus norvegicus)2314021; 2314021mRNA more ...RGD 
Experimental Diabetes Mellitus  IEP 2314021mRNA more ...RGD 
Experimental Diabetes Mellitus  ISOFas (Rattus norvegicus)2314021; 2314021protein:increased expression:heart ventricleRGD 
Experimental Diabetes Mellitus  ISOFaslg (Rattus norvegicus)2314021; 2314021protein:increased expression:heart ventricleRGD 
Experimental Diabetes Mellitus  IEP 2314021; 2314021protein:increased expression:heart ventricleRGD 
heart disease  ISOBax (Rattus norvegicus)2314021; 2314021associated with Diabetes Mellitus and ExperimentalRGD 
heart disease  IEP 2314021associated with Diabetes Mellitus and ExperimentalRGD 

Objects Annotated

Genes (Rattus norvegicus)
Bax  (BCL2 associated X, apoptosis regulator)
Ccn2  (cellular communication network factor 2)
Fas  (Fas cell surface death receptor)
Faslg  (Fas ligand)

Genes (Mus musculus)
Bax  (BCL2-associated X protein)
Ccn2  (cellular communication network factor 2)
Fas  (Fas cell surface death receptor)
Fasl  (Fas ligand)

Genes (Homo sapiens)
BAX  (BCL2 associated X, apoptosis regulator)
CCN2  (cellular communication network factor 2)
FAS  (Fas cell surface death receptor)
FASLG  (Fas ligand)


Additional Information