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Mitochondrial dynamics and mitochondrial dysfunction in mesenteric artery: role of homocysteine (867.11)
Author(s) -
Familtseva Anastasia,
Kalani Anuradha,
Kamat Pradip,
Tyagi Neetu,
Tyagi Suresh
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.867.11
Subject(s) - mitochondrial fission , mitochondrion , biology , mitochondrial fusion , cystathionine beta synthase , endocrinology , medicine , microbiology and biotechnology , mitochondrial dna , methionine , biochemistry , gene , amino acid
Many studies recently focused on the role of mitochondria in pathogenesis of vascular diseases, but little is known about influence of HHcy on the mitochondrial dynamics, whether it causes mitochondrial dysfunction and vascular alterations. We hypothesize that HHcy alters mitochondrial dynamics which leads to mitochondrial dysfunction following vascular alterations and increased blood flow resistance. To test this hypothesis, we used 12 weeks old C57BL/J6 mice (WT); Cystathionine‐β‐synthase heterozygote knockout (CBS) with genetic HHcy; C3H/HeJ (C3H), which is resistant to atherosclerosis and double‐transgenic CBS/C3H mice. Genotyping was used for the background of CBS and CBS/C3H mice. Western blot (CBS, eNOS, Mfn‐2 and Drp‐1), RT‐ PCR (Bcl‐2, BAX, caspase 3 and caspase 9), ATP/O2 consumption, mitochondrial membrane potential, blood pressure and blood flow measurements in mesenteric artery, Immunohistochemistry (CD31, connexins 40), elastin and collagen staining were also used in this study. Our data showed increase in mitochondrial fission marker (Drp‐1) and collagen in CBS compared to WT and C3H mice. In addition, we observed significant down regulation of Mfn‐2 (mitochondrial fusion marker), CD31, eNOS, connexins 40 (gap junction protein) and elastin in CBS as compared to WT and C3H mice. Interestingly, in CBS/C3H we found that fusion marker, eNOS, CD31 were increased and fission was decreased in mesentery compared to CBS mice. In addition, our data showed the signs of mitochondrial dysfunction (increased caspase 3 and 9) in CBS mice. To conclude, our data suggests that HHcy increased mitochondrial fission causing mitochondrial dysfunction and mesenteric artery alterations with increased blood flow resistance. Grant Funding Source : National Institutes of Health grants HL‐074185