Abstract

Elevated levels of plasma homocysteine (Hcy) known as hyperhomocysteinemia (HHcy), has been implicated in inflammation and remodeling of intestinal vasculature and it also aggravates the pathogenesis of inflammatory bowel disease (IBD). Interestingly, colon is the pivotal site that regulates Hcy levels in the plasma. We hypothesize that hyperhomocysteinemia decreases intestinal motility through MMP‐9 induced intestinal remodeling leading to constipation.MethodTo verify this hypothesis we used C57BL/6J or wild type (WT), CBS+/−, MMP‐9 −/− and MMP‐9−/− + Hcy mice. Intestinal motility was assessed by barium meal studies and daily feces output. Expression of ICAM‐1, iNOS, MMP‐9 and TIMPs were studied by western blot and immunohistochemistry.ResultsBarium meal studies suggest that intestinal motility is significantly decreased in CBS−/+ mice compared to other groups. Fecal output to body weight ratio was significantly reduced in CBS−/+ mice compared to other groups. There was significant up‐regulation of MMP‐9, iNOS, and ICAM‐1 expression in the colon from CBS−/+ mice compared to WT mice.ConclusionsResults suggest that HHcy decreases intestinal motility due to MMP‐9 induced intestinal remodeling leading to constipation.

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