Bone morphogenic protein antagonists are coexpressed with bone morphogenic protein 4 in endothelial cells exposed to unstable flow in vitro in mouse aortas and in human coronary arteries: role of bone morphogenic protein antagonists in inflammation and atherosclerosis.
نویسندگان
چکیده
BACKGROUND Exposure to disturbed flow, including oscillatory shear stress, stimulates endothelial cells (ECs) to produce bone morphogenic protein (BMP) 4, which in turn activates inflammation, a critical atherogenic step. BMP activity is regulated by the level of BMP antagonists. Until now it was not known whether shear also regulates the expression of BMP antagonists and whether they play a role in EC pathophysiology. METHODS AND RESULTS BMP antagonists follistatin, noggin, and matrix Gla protein were expressed in cultured bovine and human arterial ECs. Surprisingly, oscillatory shear stress increased expression of the BMP antagonists in ECs, whereas unidirectional laminar shear decreased such expression. Immunohistochemical studies with mouse aortas showed data consistent with in vitro findings: Only ECs in the lesser curvature exposed to disturbed flow, but not those in the greater curvature and straight arterial regions exposed to undisturbed flow, showed coexpression of BMP4 and the BMP antagonists. Similarly, in human coronary arteries, expression of BMP4 and BMP antagonists in ECs positively correlated with the severity of atherosclerosis. Monocyte adhesion induced by oscillatory shear stress was inhibited by knockdown of BMP4 or treatment with recombinant follistatin or noggin, whereas it was increased by knockdown of follistatin and/or noggin. CONCLUSIONS The present results suggest that ECs coexpress BMP antagonists along with BMP4 in an attempt to minimize the inflammatory response by oscillatory shear stress as part of a negative feedback mechanism. The balance between the agonist, BMP4, and its antagonists may play an important role in the overall control of inflammation and atherosclerosis.
منابع مشابه
Bone morphogenic protein receptor type 1a (BMPR1A) and Caveolin-1 associated with trastuzumab resistance of breast cancer cells
Trastuzumab is a specific monoclonal antibody used for therapeutic of the human epidermal growth factor receptor 2 (HER-2) -positive metastatic breast cancer. But, resistance to trastuzumab is a major obstacle in clinical efficiency. During the past years, several studies have been done to find the mechanisms contributing to trastuzumab resistance. Previous studies have highlighted that bone m...
متن کاملAvailable Findings Fail to Provide Strong Evidence of the Role of Bone Morphogenic Protein-2 in Femoral Head Osteonecrosis
Despite widespread research on non-traumatic femoral head osteonecrosis (FHON), there is no consensus about preventative treatment options. Insufficient blood supply and increased intra-osseous pressure are the initiating events in the majority of cases. BMPs are growth factors that belong to the transforming growth factor β (TGFβ) superfamily. Two specific formulations of BMPs have already bee...
متن کاملEffects of bone morphogenic proteins and transforming growth factor-beta on In-vitro production of endothelin-1 by human pulmonary microvascular endothelial cells.
BACKGROUND Altered endothelial cell (EC)-derived mediator levels, including increased endothelin-1 (ET-1), are hallmarks of human pulmonary arterial hypertension (PAH). Gene mutations for receptors for bone morphogenic proteins (BMP), or transforming growth factor-beta (TGF-beta) cause heritable PAH. The effects of BMPs and TGF-beta on ET-1 production by human pulmonary microvascular EC (HMVEC-...
متن کاملAn Overview of Major Genes Affecting Prolificacy in Sheep and Related Mechanisms
The objective of this review is to explore the current developments on major genes working on prolific sheep breeds and the mechanism behind it, while identifying the future working points. Productivity is the ultimate goal of farm animal production and prolificacy is a key feature in determining productivity in farm animals. Ovulation rate in mammals is an intricate process involving genetics ...
متن کاملEndothelium-derived bone morphogenic protein antagonists may counteract the proatherogenic vascular effects of bone morphogenic protein 4.
In the present issue of Circulation, Chang et al1 report novel shear stress–sensitive paracrine mechanisms that regulate the activity of bone morphogenetic proteins (BMPs) in the vascular wall. BMP2 and BMP4 are structurally related members of the transforming growth factorsuperfamily. Recent studies demonstrated that vascular endothelial and smooth muscle cells are a significant source of BMPs...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Circulation
دوره 116 11 شماره
صفحات -
تاریخ انتشار 2007