ABSTRACT
We investigated the effect of pharmacological activation of the Ca(2+)-channel transient receptor potential cation channel, subfamily V, member 4 (TRPV4) on collateral growth in a pig hind limb-ischemia model thereby identifying subcellular mechanisms. Domestic pigs received femoral artery ligature and were randomly assigned to one of the following groups (each n=6): (1) 4alpha-phorbol 12,13-didecanoate (4alphaPDD) treatment; (2) treatment with an arterio-venous shunt (AV-shunt) distal to the occlusion; or (3) implantation of NaCl-filled minipump. Six sham-operated pigs acted as controls. Aortic and peripheral mean arterial pressure (MAP) measurements were performed to assess the collateral flow index (CFI). Tissue was isolated from M. quadriceps for immunohistochemistry and from isolated collateral arteries for quantitative real time PCR (qRT-PCR). Shortly after ligature the CFI dropped from 0.96+/-0.02 to 0.21+/-0.02 in all ligature-treated groups. In ligature-only-treated pigs CFI increased to 0.56+/-0.03 after 7days. Treatment with 4alphaPDD led to an enhancement of CFI compared with ligature alone (0.73+/-0.03). CD31-staining showed improved arteriolar density. Increased Ki67 staining in collaterals indicated proliferation. qRT-PCR and Western blot analysis showed upregulation or modulation of Ca(2+)-dependent transcription factors nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1), Kv channel interacting protein 3, calsenilin (KCNIP3/CSEN/DREAM), and myocyte enhancer factor 2C (MEF2C) in 4alphaPDD- and AV-shunt-treated pigs compared with controls. Improved CFI after 4alphaPDD treatment identifies TRPV4 as an initial fluid shear-stress sensor and collateral remodelling and growth trigger. Subcellularly, modulation of Ca(2+)-dependent transcription factors indicates a pivotal role for Ca(2+)-signalling during arteriogenesis.
Subject(s)
Hindlimb/blood supply , Ischemia/physiopathology , Animals , Aorta/metabolism , Aorta/physiopathology , Arteries/metabolism , Arteries/physiopathology , Blood Vessels/metabolism , Blood Vessels/physiopathology , Calcium Signaling , Femoral Artery/metabolism , Femoral Artery/physiopathology , Femoral Artery/surgery , Hindlimb/metabolism , Hindlimb/physiopathology , Ischemia/metabolism , Lower Extremity/blood supply , Lower Extremity/physiopathology , Male , NFATC Transcription Factors/metabolism , NFATC Transcription Factors/pharmacology , Phorbols , Random Allocation , Stress, Mechanical , Sus scrofa/metabolismABSTRACT
The case of a syphilitic gumma in the cerebellopontine angle is reported. The angiographic appearance of neurosyphilis is similar to that of cerebral inflammatory processes of all varieties. The hypervascularity of the blush shown on angiography is due to hyperemia surrounding the focal necrosis. Vasoconstriction and dilatation may be seen with meningovascular syphilis and gummata. This case showed a focal hypervascularized lesion unlike the avascular lesions described in the textbooks.
