Eplerenone Reverses Age-Dependent Cardiac Fibrosis Through Downregulating Osteopontin

Background: The risk of cardiovascular disease dramatically increases with Ageing. Nowadays it is fully revealed that the fibrotic remodelling is the main cause of cardiac structural and functional changes related to the normal aging process, but the related signaling pathways and mechanisms are incompletely understood. Thus finding the new therapeutic approaches targeting cardiac fibrotic remodelling, may be necessary to develop preventive care in geriatric population against cardiovascular diseases. In this study, we evaluated the potential role of osteopontin (OPN) as novel mediators of age-dependent fibrotic pathways in heart as well as the effect of eplerenone on cardiac fibrosis reversal. Methods: Fischer-344 (F-344) rats has been used as three groups: young rats (2–3months old), aged rats (22-24 months old) without any treatment and aged rats treated with eplerenone (100 mg/kg/day) for 2 weeks. The expression level of OPN has been evaluated using real-time PCR and histological assessments were done to assess cardiac tissue fibrosis.Results: The expression level of OPN in aged rats was significantly higher than young rats and treatment with eplerenone significantly attenuated the level of OPN as well as cardiac fibrosis compare to untreated aged rats. Conclusion: Targeting cardiac fibroblast function with eplerenone could decrease expression of OPN marker and cause to reversal age-related cardiac fibrotic changes.

Effects of aging on the histology and biochemistry of rat tendon healing

Introduction Tendon diseases and injuries are a serious problem for the aged population, often leading to pain, disability and a significant decline in quality of life. The purpose of this study was to determine the influence of aging on biochemistry and histology during tendon healing and to provide a new strategy for improving tendon healing. Method A total of 24 Sprague-Dawley rats were equally divided into a young and an aged group. A rat patellar tendon defect model was used in this study. Tendon samples were collected at weeks 2 and 4, and hematoxylin-eosin, alcian blue and immunofluorescence staining were performed for histological analysis. Meanwhile, reverse transcription-polymerase chain reaction (RT-PCR) and western blot were performed to evaluate the biochemical changes. Results The histological scores in aged rats were significantly lower than those in young rats. At the protein level, collagen synthesis-related markers Col-3, Matrix metalloproteinase-1 and Metallopeptidase Inhibitor 1(TIMP-1) were decreased at week 4 in aged rats compared with those of young rats. Though there was a decrease in the expression of the chondrogenic marker aggrecan at the protein level in aged tendon, the Micro-CT results from weeks 4 samples showed no significant difference(p>0.05) on the ectopic ossification between groups. Moreover, we found more adipocytes accumulated in the aged tendon defect with the Oil Red O staining and at the gene and protein levels the markers related to adipogenic differentiation. Conclusions Our findings indicate that tendon healing is impaired in aged rats and is characterized by a significantly lower histological score, decreased collagen synthesis and more adipocyte accumulation in patellar tendon after repair.

CONTENT OF GROWTH FACTORS AND HYPOXIA-INDUCIBLE FACTOR IN THE SKIN OF RATS OF DIFFERENT AGE AFTER WOUND HEALING

The aim of the study was to determine the content of vascular endothelial growth factor (VEGF), nerve growth factor (NGF) and hypoxia-inducible factor-1alpha (HIF- 1α) in the skin of 40 female rats of different ages (3 and 12 mo) after closure of the wound bed. In each age group composed of 20 rats, 10 rats served as a control group, and in remaining rats a facelift operation was performed and cut wounds on the anterior abdominal wall (5 cm × 0.5 cm) were simulated. The duration of wound surface healing in rats of different age groups was recorded. On the day of complete healing, the animals were killed, and the skin was cut in the areas of the former wound bed. In control rats, the skin was excised in the same places. The content of VEGF, NGF and HIF-1α was determined in the skin by enzyme- linked immunosorbent assay. It was found that in the group of young (3-month-old) rats, complete healing of the wound surface after facelift surgery occurred after 14.0 ± 1.0 days, and on the anterior abdominal wall - after 13.0 ± 1.0 days. In 12-month-old rats, the duration of wound surface healing after facelift surgery and incised wound on the anterior abdominal wall increased to 17.0 ± 1.5 days. In the former wound bed, the content of HIF-1α in young rats increased by 60.7%, and in 12-month-old rats - by 231.6%. In the former wound bed, the content of VEGF and NGF in young rats increased by 14.8 and 11.7%, respectively, and in 12-month-old rats - by 182.4 and 152.6%, respectively. It was concluded that more pronounced hypoxia in the skin after surgery in 12-month-old rats may be the cause of postoperative complications.