Shweta Singh1, Hien C Nguyen2,3, Mehroz Ehsan2,4, David C R Michels2, Priyanka Singh4, Mohammad Qadura5,6, Krishna K Singh2,3,6,7. 1. Department of Chemical and Biochemical Engineering, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada. 2. Department of Medical Biophysics, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada. 3. Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada. 4. Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada. 5. Vascular Surgery, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON, Canada. 6. Institute of Medical Science, University of Toronto, Toronto, ON, Canada. 7. Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
Abstract
OBJECTIVE: Atherosclerosis is the main cause of the cardiovascular disease (CVD). Elevated blood cholesterol and inflammation of the endothelium are two major mechanisms contributing to the establishment of atherosclerotic plaques. Statins, such as pravastatin, are blood-cholesterol lowering drugs commonly prescribed for patients with or at risk for CVDs. In addition to lowering blood cholesterols, statins have recently been shown to improve endothelial function in both hyper- and normocholesterolemic patients with atherosclerosis. To understand the molecular mechanisms underlying the endothelial function improvement by statins, we assessed the RNA profile of pravastatin-treated endothelial cells, particularly their mRNAs and long non-coding RNAs (lncRNAs). METHODS: Human umbilical vein endothelial cells (HUVECs) treated with pravastatin (10 µM) for 24 hr were profiled for lncRNAs and mRNAs using the Arraystar Human lncRNA Expression Microarray V3.0. RESULTS: Of the 30,584 different lncRNAs screened, 95 were significantly upregulated, while 86 were downregulated in HUVECs responding to pravastatin. LINC00281 and BC045663 were the most upregulated (~8-fold) and downregulated (~3.5-fold) lncRNAs, respectively. Of the 26,106 different mRNAs screened in the pravastatin-treated HUVEC samples, 190 were significantly upregulated, while 90 were downregulated. Assigning the differentially expressed genes by bioinformatics into functional groups revealed their molecular signaling involvement in the following physiological processes: osteoclast differentiation, Rap1 signaling pathway, hematopoiesis, immunity, and neurotrophin signaling pathway. CONCLUSIONS: This is the first lncRNA and mRNA expression profiling of pravastatin-mediated changes in human endothelial cells. Our results reveal potential novel targets and mechanisms for pravastatin-mediated vascular protection in atherosclerosis.
OBJECTIVE: Atherosclerosis is the main cause of the cardiovascular disease (CVD). Elevated blood cholesterol and inflammation of the endothelium are two major mechanisms contributing to the establishment of atherosclerotic plaques. Statins, such as pravastatin, are blood-cholesterol lowering drugs commonly prescribed for patients with or at risk for CVDs. In addition to lowering blood cholesterols, statins have recently been shown to improve endothelial function in both hyper- and normocholesterolemic patients with atherosclerosis. To understand the molecular mechanisms underlying the endothelial function improvement by statins, we assessed the RNA profile of pravastatin-treated endothelial cells, particularly their mRNAs and long non-coding RNAs (lncRNAs). METHODS: Human umbilical vein endothelial cells (HUVECs) treated with pravastatin (10 µM) for 24 hr were profiled for lncRNAs and mRNAs using the Arraystar Human lncRNA Expression Microarray V3.0. RESULTS: Of the 30,584 different lncRNAs screened, 95 were significantly upregulated, while 86 were downregulated in HUVECs responding to pravastatin. LINC00281 and BC045663 were the most upregulated (~8-fold) and downregulated (~3.5-fold) lncRNAs, respectively. Of the 26,106 different mRNAs screened in the pravastatin-treated HUVEC samples, 190 were significantly upregulated, while 90 were downregulated. Assigning the differentially expressed genes by bioinformatics into functional groups revealed their molecular signaling involvement in the following physiological processes: osteoclast differentiation, Rap1 signaling pathway, hematopoiesis, immunity, and neurotrophin signaling pathway. CONCLUSIONS: This is the first lncRNA and mRNA expression profiling of pravastatin-mediated changes in human endothelial cells. Our results reveal potential novel targets and mechanisms for pravastatin-mediated vascular protection in atherosclerosis.
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