{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T07:18:27Z","timestamp":1792739907972,"version":"4.5.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2009,7,2]]},"abstract":"<jats:p>\n            The capacity of the collateral circulation to lessen injury in occlusive vascular disease depends on the density and caliber of native (preexisting) collaterals, as well as their ability to outwardly remodel in ischemia. Native collateral conductance varies widely among healthy individuals, yet little is known about what specifies collateral formation. Chloride intracellular channel (CLIC)4 protein is required for endothelial cell hollowing, a process necessary for vessel formation during embryogenesis and ischemia. Whether CLIC4 has other physiological roles in vascular biology is uncertain. We studied collateral formation and remodeling in mice deficient in CLIC1 and CLIC4. Vascular responses to femoral artery ligation were similar in\n            <jats:italic>Clic1<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            and wild-type mice. In contrast, immediately after ligation perfusion dropped more in\n            <jats:italic>Clic4<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            than wild-type mice, suggesting fewer preexisting collaterals, a finding confirmed by angiography, greater ischemia, and worse recovery of perfusion; however, collateral remodeling was unaffected. Likewise, native cerebral collateral density in\n            <jats:italic>Clic4<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            (but not\n            <jats:italic>Clic1<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            ) mice was reduced, resulting in severe infarctions. This was associated with impaired perinatal formation and stabilization of nascent collaterals.\n            <jats:italic>Clic4<\/jats:italic>\n            hemizygous mice had intermediate deficits in the above parameters, suggesting a gene-dose effect. Ischemia augmented CLIC1 and CLIC4 expression similarly in wild-type mice. However, CLIC1 increased 3-fold more in\n            <jats:italic>Clic4<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice, suggesting compensation. Despite greater ischemia in\n            <jats:italic>Clic4<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice, hypoxia-inducible factor-1\u03b1, vascular endothelial growth factor (VEGF) and angiopoietin-2 increased less compared to wild-type, suggesting CLIC4 exerts influences upstream of hypoxia-inducible factor-1\u03b1-VEGF signaling. Hence, CLIC4 represents the second gene that, along with VEGF shown by us previously, specifies native collateral formation.\n          <\/jats:p>","DOI":"10.1161\/circresaha.109.197145","type":"journal-article","created":{"date-parts":[[2009,5,29]],"date-time":"2009-05-29T01:54:54Z","timestamp":1243562094000},"page":"89-98","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":74,"title":["Chloride Intracellular Channel-4 Is a Determinant of Native Collateral Formation in Skeletal Muscle and Brain"],"prefix":"10.1161","volume":"105","author":[{"given":"Dan","family":"Chalothorn","sequence":"first","affiliation":[{"name":"From the Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Zhang","sequence":"additional","affiliation":[{"name":"From the Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer E.","family":"Smith","sequence":"additional","affiliation":[{"name":"From the Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Edwards","sequence":"additional","affiliation":[{"name":"From the Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Faber","sequence":"additional","affiliation":[{"name":"From the Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(00)00281-9"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1080\/mic.10.1.83.97"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2006.05.046"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-008-0760-x"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000066321.03474.da"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.107.703959"},{"key":"e_1_3_3_7_2","unstructured":"Fernandez B. Development of collateral arteries. In: Schaper W Schaper J eds. Arteriogenesis. Boston Mass: Kluwer Academic; 2004 pp 11\u201319."},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.108.181115"},{"key":"e_1_3_3_9_2","doi-asserted-by":"crossref","unstructured":"Ruhrberg C Gerhardt H Golding M Watson R Ioannidou S Fujisawa H Betsholtz C Shima DT. Spatially restricted patterning cues provided by heparin-binding VEGF-A control blood vessel branching morphogenesis. 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Challenging accepted ion channel biology: p64 and the CLIC family of putative intracellular anion channel proteins. Mol Membr Biol. 2003; 20: 1\u201311.","journal-title":"Mol Membr Biol"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/mc.20324"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00952.2004"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00047.2007"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm740"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.0000181075.77897.0e"},{"key":"e_1_3_3_25_2","unstructured":"Zhang H Keum S Marchuk D Sealock R Faber JE. Analysis of 19 mouse strains demonstrates that genetic variations in pial collateral dimensions are the major determinants of severity of infarct volume after middle cerebral artery occlusion (MCAO). Cardiovasc Revasc Med J. 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