title: Exposure to endosulfan increases endothelial permeability by transcellular and paracellular pathways in relation to cardiovascular diseases.
abstract: Exposure to environmental pollutants results in out-of-balance of vascular homeostasis. Endothelial dysfunction leads to a disruption of the endothelial permeability characteristics, associated with cardiovascular diseases. We previously reported that endosulfan could cause endothelial dysfunction, but the role of endosulfan in permeability of endothelial cells has been unexplored. To elucidate molecular mechanism of endosulfan-induced changes in endothelial permeability, human umbilical vein endothelial cells (HUVECs) were exposed to endosulfan, followed by endothelial permeability analysis. The results showed that permeability of HUVECs was enhanced at 48 h after exposure to endosulfan in a dose-dependent manner. Immunofluorescence analysis demonstrated the disruptions of actin cytoskeleton and focal adhesion in endosulfan-exposed cells. Endosulfan activated MMP3/LAMC1/FAK signaling pathway, and downregulated ROCK and PXN in transcellular pathway. Endosulfan affected adherens junctions via E-cadherin and β-catenin, and impaired gap junctions through downregulation of Cx43 in paracellular pathway. We predicted four closely related human cardiovascular diseases in Nextbio, including shock, coronary arteriosclerosis, disorder of cardiac function and hypertensive disorder in relation to endosulfan exposure. Some genes such as ROCK2 and PXN were predicted to be key genes in these diseases. These findings suggest that endosulfan increased endothelial permeability by paracellular and transcellular pathways, implicating the potential correlation between endosulfan and cardiovascular diseases.
authors.affiliation: Institute of Environmental Systems Biology, Dalian Maritime University, Linghai Road 1, Dalian, 116026, PR China. Electronic address: jotan1995@163.com.
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.affiliation: Institute of Environmental Systems Biology, Dalian Maritime University, Linghai Road 1, Dalian, 116026, PR China. Electronic address: liutong_555@163.com.
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.affiliation: Institute of Environmental Systems Biology, Dalian Maritime University, Linghai Road 1, Dalian, 116026, PR China. Electronic address: limeitwo@163.com.
authors.forename: Limei
authors.initials: L
authors.lastname: Lin
authors.affiliation: Institute of Environmental Systems Biology, Dalian Maritime University, Linghai Road 1, Dalian, 116026, PR China. Electronic address: lishuai19891115@163.com.
authors.forename: Shuai
authors.initials: S
authors.lastname: Li
authors.affiliation: Institute of Environmental Systems Biology, Dalian Maritime University, Linghai Road 1, Dalian, 116026, PR China. Electronic address: hangxmdl@163.com.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Hang
authors.affiliation: Institute of Environmental Systems Biology, Dalian Maritime University, Linghai Road 1, Dalian, 116026, PR China. Electronic address: yqsun@dlmu.edu.cn.
authors.forename: Yeqing
authors.initials: Y
authors.lastname: Sun
mesh_terms: D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D004726:Endosulfan / Q000633:toxicity*; D042783:Endothelial Cells / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D010539:Permeability / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D007306:Insecticides; D004726:Endosulfan
keywords: Actin cytoskeleton; Cardiovascular diseases; Endosulfan; Endothelial permeability; Interendothelial junctions