Sequential changes in autophagy in diabetic cardiac fibrosis

Abstract

Abstract. Autophagy is considered to be associated with cardiac fibrosis. However, whether autophagy accelerates or ameliorates fibrosis remains to be elucidated. In the present study, 36 rats were divided into two groups: Control rats and diabetic rats. The diabetic rats were established by feeding the animals a high fat diet combined with streptozotocin. From the two groups, six rats were sacrificed after 1, 6 and 7 months. Cardiac systolic functions were measured. The collagen volume fraction was calculated using Masson's trichome staining and the mRNA expression levels of type-I and type-III collagen were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to assess the levels of cardiac fibrosis. The protein contents of microtubule-associated protein 1 light chain 3 (LC3) and sequestosome 1 (P62) were evaluated using western blotting, and the mRNA expression of Beclin 1 was measured using RT-qPCR, in order to assess autophagy. The results revealed that, in the diabetic rats, cardiac fibrosis developed and cardiac systolic function was reduced. In the hearts of the diabetic rats, the mRNA expression levels of collagen type I and III, and Beclin1 were upregulated; the ratio of the protein level of LC3-II/LC3-I was increased and the content of P62 was decreased. All the changes were aggravated as time increased. The changes in autophagy were correlated with those of cardiac fibrosis, suggesting that autophagy may have a synergistic role in diabetic cardiac fibrosis.

Rho‐Kinase inhibitor fasudil suppresses high glucose‐induced H9c2 cell apoptosis through activation of autophagy

“…Fasudil inhibited the induction of ROCK1 and ROCK2 mRNA levels. This finding is consistent with previous studies that reported activation of ROCK by high glucose and inhibition of ROCK by fasudil . Thus, the data indicate that fasudil inhibits ROCK by decreasing its expression.…”

“…In response to malnutrition, autophagosomes chelate reactive oxygen species (ROS)‐generating mitochondria to protect cells, while 3‐MA increases the production of ROS and advances apoptosis . Our previous study demonstrated that autophagy‐related protein expression was increased in diabetic rat hearts . Interestingly, in the current study, 3‐MA reversed fasudil's effects on cell proliferation and apoptosis.…”

“…Autophagy, one of the most important regulatory targets of cellular energy metabolism and cell survival, plays an end‐effector role in the development of heart disease and prognosis . In our previous study, we demonstrated that autophagy and apoptosis have a synergistic role in diabetic cardiac fibrosis . However, the function of autophagy in promoting or ameliorating cell apoptosis in diabetic cardiomyopathy remains unresolved.…”

“…13 In our previous study, we demonstrated that autophagy and apoptosis have a synergistic role in diabetic cardiac fibrosis. 14 Fasudil, a ROCK inhibitor, has been shown to suppress cardiac cell apoptosis caused by ischemia/reperfusion injury. 4,15,16 Fasudil can also suppress diabetic cardiac fibrosis 17,18 and matrix remodeling in diabetic nephropathy.…”

Proteostasis in epicardial versus subcutaneous adipose tissue in heart failure subjects with and without diabetes

“…We observed a significant increase of LC3-I in EAT which may indicate that EAT has more capacity for macroautophagy than SAT. Moreover, the levels of LC3-II in EAT were also significantly increased, and together with the increase of Beclin 1 and P-AMPK, these results are suggestive of an increased autophagy in EAT compared to SAT, in agreement with previous studies [101-103]. As mentioned before, EAT exhibits increased ER stress and, as such, increase in misfolded or dysfunctional proteins.…”