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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:1753.)
© 2000 American Heart Association, Inc.

Vascular Biology

Multiple Connexin Expression in Regenerating Arterial Endothelial Gap Junctions

Hung-I Yeh; Yu-Jun Lai; Hao-Min Chang; Yu-Shien Ko; Nicholas J. Severs; Cheng-Ho Tsai

From Mackay Memorial Hospital (H.-I.Y., Y.-J.L., H.-M.C., C.-H.T.), Taipei Medical College, and the First Cardiovascular Division (Y.-S.K.), Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan; and the National Heart and Lung Institute (Y.-S.K., N.J.S.), Imperial College School of Medicine, London, UK.

Correspondence to Cheng-Ho Tsai, Cardiac Medicine, Mackay Memorial Hospital, 92, Sec 2, North Chung San Road, Taipei 10449, Taiwan. E-mail cht7678{at}ms2.mmh.org.tw

Abstract—Endothelial cells form gap junctions that, according to vessel type, may be composed of up to 3 types of connexin, connexin37, connexin40, and connexin43. Although changes in connexin expression have been linked to growth and injury in cultured endothelial cells, information on connexin expression in regenerating endothelium in situ is lacking. We investigated gap junction distribution and expression of all 3 endothelial connexins during healing in rat carotid artery after denudation injury. En face viewing of the vascular luminal surface by means of immunoconfocal microscopy was used to examine the spatial and temporal expression pattern of the endothelial connexins. Gap junction spots labeled by specific antisera against connexin37, connexin40, and connexin43 were quantified 7, 14, and 28 days after injury, and the relations among the connexins were examined by using colocalization analysis. Complementary electron microscopy was also conducted. After injury, the regenerating endothelium initially expressed small, sparse gap junctions, the numbers of which progressively increased to values equivalent to those of controls. Although connexin40 gap-junctional spot size and area returned to uninjured levels by 28 days after injury, connexin37 and connexin43 spot size and area exceeded those of the uninjured artery (P<0.05). Double-label analysis showed that even though colocalization of connexins to the same gap-junctional spot is a common feature, the extent of colocalization was time dependent (>80% in the intact artery at postinjury day 28 and <70% at postinjury days 7 and 14, P<0.01). We conclude that distinct alterations in expression of the 3 connexins are associated with regeneration of the arterial endothelium in situ, implying different intercellular communication requirements during the various phases of the healing process.

Key Words: gap junctions • connexin • endothelial cells • regeneration

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