Abstract
BackgroundCardiovascular 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 findings40 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-α, 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.ConclusionMMP-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.
Highlights
Obesity is a major risk factor for Cardiovascular diseases (CVD)
A strong cross talk exists between Matrix Metalloproteinase 9 (MMP-9), cytokine production and macrophage function
It plays an important regulatory role in osteoclastogenesis. It may be a key molecule in charge for coupling CVD and bone diseases in high fat diet fed rats
Summary
Obesity is a major risk factor for CVD. Even in the absence of other risk factors, obesity has been considered a strong independent predictor of CVD [1].On the other hand, obesity has been thought to be protective against osteoporosis. Obesity is a major risk factor for CVD. Even in the absence of other risk factors, obesity has been considered a strong independent predictor of CVD [1]. The recent clinical and epidemiologic reports have illustrated a higher incidence of osteoporosis and bone fractures in obese individuals than in individuals within the normal weight range [2,3,4]. The complex relationship between obesity and osteoporosis is currently unclear. Cardiovascular diseases (CVD) represent one of the major sequelae of obesity. 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, the precise molecular pathways underlying this close association remain poorly understood. The present work aimed to study Matrix Metalloproteinase 9 (MMP-9), as a proposed link between atherosclerosis and osteoporosis in high fat diet fed rats
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