br Sources of funding This work
Sources of funding This work was supported by grants from the Canadian Institutes of Health Research (CIHR) (No. MOP-111096) and from the Heart and Stroke Foundation of Canada awarded to Dr. Danielle Jacques.
Introduction A large number of epidemiological, human and experimental animal studies in general support an association of periodontitis with cardiovascular disease (Friedewald et al., 2009). Thus, DNA-traces of oral bacteria in coronary and carotid atheromas (Chiu, 1999, Fiehn et al., 2005, Haraszthy et al., 2000) have led to the hypothesis, that oral bacteria might be a possible causative factor for atherosclerosis development (Brodala et al., 2005, Jain et al., 2003, Lalla et al., 2003, Li et al., 2002). Periodontitis is a chronic oral infection caused by bacteria in the gingival pocket. Gram-negative Z-Guggulsterone bacteria play a key role in periodontal disease progression, and Porphyromonas gingivalis (P.g.) is considered one of the most pathogenic species (Griffen et al., 1998, Loesche, 1993, Socransky and Haffajee, 2002). The infection can lead to activation of a host response involving innate immune components followed by recruitment of adaptive immunity. Moreover, an active transfer of oral bacteria and their products such as lipopolysaccarides (LPS) to the bloodstream is enhanced by inflammatory changes of the gingival tissue including ulceration of the pocket epithelium (Forner et al., 2006b, Geerts et al., 2002, Ide et al., 2004, Lofthus et al., 1991, Silver et al., 1977). Endothelial dysfunction is considered a common pathway by which risk factors such as inflammation may influence atherogenesis. Thus, a recent study showed that intensive periodontal treatment of periodontitis patients resulted in enhanced periodontal health associated with significantly improved endothelial function and vasodilatation (Smeeth et al., 2004, Tonetti et al., 2007). However, it is unknown whether increased plasma levels of oral pathogens may result in endothelial dysfunction with vasoconstriction in periodontitis patients. A suitable method for studies of receptor profile changes in arteries is the organ culture method. Thus, previous studies have verified an endothelin ETB receptor upregulation on smooth muscle cells in arteries after 24h of organ culture (Adner et al., 1996, Nilsson et al., 2008a, Nilsson et al., 2008b, Stenman et al., 2002, Wackenfors et al., 2004). We now hypothesize that P.g. can alter the gene expression in coronary arteries, which may be shown by the organ culture method. Therefore, we exposed coronary arteries to LPS from P.g. and recorded the vasomotor response to the selective ETB receptor agonist Sarafotoxin 6c, and the protein expression was studied by immunohistochemistry. The main aim of the present study was to learn whether LPS influences the contractile responses of coronary arteries after 24h organ culture.
Materials and methods
Discussion An association between periodontitis and cardiovascular disease may be based on a continued release of bacteria and/or their LPS from the gingival pockets to the bloodstream due to daily procedures such as chewing (Forner et al., 2006a), tooth brushing (Olsen, 2008) and dental flossing (Crasta et al., 2009). P.g. is a Gram-negative anaerobic rod important in the pathogenesis of periodontitis. The bacterium produces several virulence factors including LPS, which can lead to tissue destruction. In mammals three isoforms of endothelin mainly produced by endothelium have been described including ET-1, ET-2 and ET-3, all with vasoconstrictor and pressor properties (Inoue et al., 1989). Sarafotoxines (i.e. S6c) are peptides resembling ET-1 in terms of structure and function (Kloog et al., 1988). The two endothelin receptor subtypes ETA and the ETB belonging to the seven transmembrane G-protein couple receptor family (Arai et al., 1990, Sakurai et al., 1990) participate in the balance between vasodilatation and vasoconstriction of the artery wall. The effect of endothelin is mediated by ETA and ETB receptors mainly located on the vascular smooth muscle cells and endothelial cells, respectively. ET-1 elicits a contractile response through the ETA receptor located on vascular smooth muscle cells by activating protein kinase C (PKC) and intracellular release of calcium (Danthuluri and Brock, 1990). The activation of ETB receptors on endothelial cells mediates vasodilatation through release of nitric oxide from the endothelium (Szok et al., 2001).