Acute-phase protein haptoglobin is a cell migration factor involved in arterial restructuring.
Collagen turnover and cell migration are fundamental aspects of arterial restructuring. To identify mRNAs involved in blood flow-induced arterial restructuring, we performed subtraction polymerase chain reaction and found expression of haptoglobin mRNA in adventitial fibroblasts of rabbit arteries. Haptoglobin is highly expressed in liver, but its arterial expression and function are unknown. In vitro studies revealed that stimulation of haptoglobin expression by lipopolysaccharides in mice fibroblasts stimulated migration of wild-type fibroblasts but had no effect on migration of haptoglobin knockout fibroblasts. In vivo studies showed that flow-induced arterial restructuring was delayed in haptoglobin knockout mice. This new function of haptoglobin might be explained by facilitating cell migration through accumulation of a temporary gelatin matrix because cell culture showed that haptoglobin is involved in the breakdown of gelatin. We conclude that haptoglobin is highly expressed in arterial tissue and is involved in arterial restructuring. This new haptoglobin function may also apply to other functional and pathological restructuring processes such as angiogenesis, tissue repair, and tumor cell invasion.
de Kleijn
Dominique P V
DP
Experimental Cardiology Laboratory, University Medical Center, Utrecht, The Netherlands. D.deKleijn@hli.azu.nl
Smeets
Mirjam B
MB
Kemmeren
Patrick P C W
PP
Lim
Sai K
SK
Van Middelaar
Ben J
BJ
Velema
Evelyn
E
Schoneveld
Arjan
A
Pasterkamp
Gerard
G
Borst
Cornelius
C
D000595:Amino Acid Sequence; D000818:Animals; D001158:Arteries / Q000033:anatomy & histology* / Q000737:chemistry / Q000502:physiology; D017536:Carotid Artery, Common; D002460:Cell Line; D002465:Cell Movement; D002630:Chemotactic Factors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D003094:Collagen / Q000378:metabolism; D005347:Fibroblasts / Q000502:physiology; D006242:Haptoglobins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008026:Ligation; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits
D002630:Chemotactic Factors; D006242:Haptoglobins; D012333:RNA, Messenger; D003094:Collagen; D020782:Matrix Metalloproteinases