Dataset Information

Matrix metalloproteinase 9 a potential major player connecting atherosclerosis and osteoporosis in high fat diet fed rats.

ABSTRACT:

Background

Cardiovascular diseases (CVD) represent one of the major sequelae of obesity. On the other hand, the relationship between bone diseases and obesity remains unclear. An increasing number of biological and epidemiological studies suggest the presence of a link between atherosclerosis and osteoporosis, however, the precise molecular pathways underlying this close association remain poorly understood. The present work thus aimed to study Matrix Metalloproteinase 9 (MMP-9), as a proposed link between atherosclerosis and osteoporosis in high fat diet fed rats.

Methods and findings

40 rats were randomly divided into 4 groups: control, untreated atherosclerosis group, atherosclerotic rats treated with carvedilol (10mg/kg/d) and atherosclerotic rats treated with alendronate sodium (10mg/kg/d). After 8 weeks, blood samples were collected for estimation of Lipid profile (Total cholesterol, HDL, TGs), inflammatory markers (IL-6, TNF-?, CRP and NO) and Bone turnover markers (BTMs) (Alkaline phosphatase, osteocalcin and pyridinoline). Rats were then euthanized and the aortas and tibias were dissected for histological examination and estimation of MMP-9, N-terminal propeptide of type I procollagen (PINP), C-terminal telopeptide of type I collagen (CTX) and NF-kB expression. Induction of atherosclerosis via high fat diet and chronic stress induced a significant increase in BTMs, inflammatory markers and resulted in a state of dyslipidaemia. MMP-9 has also shown to be significantly increased in the untreated atherosclerosis rats and showed a significant correlation with all measured parameters. Interestingly, Carvedilol and bisphosphonate had almost equal effects restoring the measured parameters back to normal, partially or completely.

Conclusion

MMP-9 is a pivotal molecule that impact the atherogenic environment of the vessel wall. A strong cross talk exists between MMP-9, cytokine production and macrophage function. It also plays an important regulatory role in osteoclastogenesis. So, it may be a key molecule in charge for coupling CVD and bone diseases in high fat diet fed rats. Therefore, we suggest MMP-9 as a worthy molecule to be targeted pharmacologically in order to control both conditions simultaneously. Further studies are needed to support, to invest and to translate this hypothesis into clinical studies and guidelines.

SUBMITTER: Sabry M

PROVIDER: S-EPMC7877768 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Matrix metalloproteinase 9 a potential major player connecting atherosclerosis and osteoporosis in high fat diet fed rats.

Sabry Maha M Mostafa Seham S Rashed Laila L Abdelgwad Marwa M Kamar Samaa S Estaphan Suzanne S

PloS one 20210211 2

<h4>Background</h4>Cardiovascular diseases (CVD) represent one of the major sequelae of obesity. On the other hand, the relationship between bone diseases and obesity remains unclear. An increasing number of biological and epidemiological studies suggest the presence of a link between atherosclerosis and osteoporosis, however, the precise molecular pathways underlying this close association remain poorly understood. The present work thus aimed to study Matrix Metalloproteinase 9 (MMP-9), as a pr ...[more]

PMID: 33571214

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Project description:Atherosclerosis and its associated cardiovascular diseases (CVDs) are serious threats to human health and have been reported to be associated with the gut microbiota. Recently, the role of berberine (BBR) in atherosclerosis and gut microbiota has begun to be appreciated. The purposes of this study were to observe the effects of high or low doses of BBR on atherosclerosis and gut microbiota modulation, and to explore their correlation in ApoE-/- mice fed a high-fat diet. A significant decrease in atherosclerotic lesions was observed after treatment with BBR, with the effect of the high dose being more obvious. Both BBR treatments significantly reduced total cholesterol, APOB100, and very low-density lipoprotein cholesterol levels but levels of high/low-density lipoprotein cholesterol and lipoprotein (a) were only reduced by high-dose BBR. Decreased pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin (IL)-1?, IL-6 and increased anti-inflammatory IL-10 and adiponectin levels were observed in the high-dose BBR group, but no decrease in IL-6 or increase in IL-10 was evident using the low-dose of BBR. 16S rRNA sequencing showed that BBR significantly altered the community compositional structure of gut microbiota. Specifically, BBR enriched the abundance of Roseburia, Blautia, Allobaculum, Alistipes, and Turicibacter, and changed the abundance of Bilophila. These microbiota displayed good anti-inflammatory effects related to the production of short-chain fatty acids (SCFAs) and were related to glucolipid metabolism. Alistipes and Roseburia were significantly enriched in high-dose BBR group while Blautia and Allobaculum were more enriched in low-dose, and Turicibacter was enriched in both BBR doses. Metagenomic analysis further showed an elevated potential for lipid and glycan metabolism and synthesis of SCFAs, as well as reduced potential of TMAO production after BBR treatment. The findings demonstrate that both high and low-dose BBR can improve serum lipid and systemic inflammation levels, and alleviate atherosclerosis induced by high-fat diet in ApoE-/- mice. The effects are more pronounced for the high dose. This anti-atherosclerotic effect of BBR may be partly attributed to changes in composition and functions of gut microbiota which may be associated with anti-inflammatory and metabolism of glucose and lipid. Notably, gut microbiota alterations showed different sensitivity to BBR dose.

Dataset Information

Matrix metalloproteinase 9 a potential major player connecting atherosclerosis and osteoporosis in high fat diet fed rats.

Background

Methods and findings

Conclusion

Publications

Matrix metalloproteinase 9 a potential major player connecting atherosclerosis and osteoporosis in high fat diet fed rats.

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