Subscribe to RSS
DOI: 10.1160/TH06-05-0263
Elevated complement C3 is associated with early restenosis after eversion carotid endarterectomy
Financial support: These studies were supported by the Ministry of Welfare (ETT 522/2003), the National Research Fund of Hungary (OTKA T049266, OTKA T046837) and the EC ATHERNET (QLG1-CT-2002–90397).Publication History
Received
14 May 2006
Accepted after resubmission
05 August 2006
Publication Date:
29 November 2017 (online)
Summary
Early restenosis following carotid endarterectomy (CEA) is an inflammatory process leading to myointimal hyperplasia of smooth muscle cells. The risk for restenosis is increased in homozygous carriers of the normal (A) allele of mannose-binding lectin (MBL2) gene. Our objective was to study the associ-ations of C3 and as control three non-complement acute-phase reactants (APRs) (C-reactive protein, haptoglobin and α2HS-glycoprotein) with early restenosis following CEA.We also considered, whether MBL2 genotype relates to C3 levels and to the risk of restenosis. Concentrations of the APRs were determined by radial immunodiffusion or immunoturbidimetric methods in 64 patients who underwent eversion CEA and were followed up with carotid duplex scan (CDS) examinations for at least one year. MBL2 genotypes were determined by a PCR-SSP method. C3 levels increased during the follow-up and correlated with the percentage of restenosis detected by CDS at 14 months postsurgery, in MBL2 A/A allele carriers. Patients with high C3 levels had nearly five-fold higher odds for the presence of significant restenosis (>50% reduction in diameter) even after adjusting for MBL2 genotype, age and gender. By contrast, no such associations were detected between the non-complement APRs and early restenosis. C3 is associated with and might have a direct role in the development of an early restenosis following CEA, which is partially related to an intact MBL lectin pathway, thus determining C3 levels might have clinical importance. On the other hand, our results indicate that the regulation of C3 differs from non-complement APRs.
-
References
- 1 Bond R, Rerkasem K, Rothwell PM. Systematic review of the risks of carotid endarterectomy in relation to the clinical indication for and timing of surgery. Stroke 2003; 34: 2290-301.
- 2 Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. J Am Med Assoc 1995; 273: 1421-8.
- 3 Hunter GC, Edgar J. Poth Memorial/ WL Gore and Associates Inc Lectureship The clinical and pathological spectrum of recurrent carotid stenosis. Am J Surg 1997; 174: 583-8.
- 4 Frericks H, Kievit J, van Baalen JM. et al. Carotid recurrent stenosis and risk of ipsilateral stroke: a systematic review of the literature. Stroke 1998; 29: 244-50.
- 5 Zierler RE, Bandyk DF, Thiele BL. et al. Carotid artery stenosis following endarterectomy. Arch Surg 1982; 117: 1408-15.
- 6 Ricotta JJ, O’Brien MS, DeWeese JA. Natural history of recurrent and residual stenosis after carotid endarterectomy: implications for postoperative surveillance and surgical management. Surgery 1992; 112: 656-61 discussion 62-3.
- 7 Trisal V, Paulson T, Hans SS. et al. Carotid artery restenosis: an ongoing disease process. Am Surg 2002; 68: 275-9 discussion 9-80.
- 8 Rugonfalvi-Kiss S, Dósa E, Madsen HO. et al. High rate of early restenosis after carotid eversion endarterectomy in homozygous carriers of the normal mannose-binding lectin genotype. Stroke 2005; 36: 944-8.
- 9 Dósa E, Rugonfalvi-Kiss S, Prohászka Z. et al. Marked decrease in the levels of two inflammatory markers, hs-C-reactive protein and fibrinogen in patients with severe carotid atherosclerosis after eversion carotid endarterectomy. Inflamm Res 2004; 53: 631-5.
- 10 Lin ZH, Fukuda N, Jin XQ. et al. Complement 3 is involved in the synthetic phenotype and exaggerated growth of vascular smooth muscle cells from spontaneously hypertensive rats. Hypertension 2004; 44: 42-7.
- 11 Muscari A, Bozzoli C, Puddu GM. et al. Association of serum C3 levels with the risk of myocardial infarction. AmJ Med 1995; 98: 357-64.
- 12 Ajjan R, Grant PJ, Futers TS. et al. Complement C3 and C-reactive protein levels in patients with stable coronary artery disease. Thromb Haemost 2005; 94: 1048-53.
- 13 Biller J, Feinberg WM, Castaldo JE. et al. Guidelines for carotid endarterectomy: a statement for healthcare professionals from a Special Writing Group of the Stroke Council, American Heart Association. Circulation 1998; 97: 501-9.
- 14 Entz L, Járányi Z, Nemes A. Comparison of perioperative results obtained with carotid eversion endarterectomy and with conventional patch plasty. Cardiovasc Surg 1997; 05: 16-20.
- 15 Entz L, Járányi S, Nemes A. Eversion endarterectomy in surgery of the internal carotid artery. Cardiovasc Surg 1996; 04: 190-4.
- 16 Kohler PF, Muller-Eberhard HJ. Immunochemical quantitation of the third, fourth and fifth components of human complement: concentrations in the serum of healthy adults. J Immunol 1967; 99: 1211-6.
- 17 Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16: 1215.
- 18 Garred P, Strom JJ, Quist L. et al. Association of mannose-binding lectin polymorphisms with sepsis and fatal outcome, in patients with systemic inflammatory response syndrome. J Infect Dis 2003; 188: 1394-403.
- 19 Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 1999; 340: 448-54.
- 20 Legoedec J, Gasque P, Jeanne JF. et al. Expression of the complement alternative pathway by human myoblasts in vitro: biosynthesis of C3, factor B, factor H and factor I. Eur J Immunol 1995; 25: 3460-6.
- 21 Ueda Y, Nagasawa K, Tsukamoto H. et al. Production of the third and fourth component of complement (C3, C4) by smooth muscle cells. Immunology 1996; 89: 183-8.
- 22 Ikeda U, Ikeda M, Oohara T. et al. Interleukin 6 stimulates growth of vascular smooth muscle cells in a PDGF-dependent manner. Am J Physiol 1991; 260: H1713-7.
- 23 Selzman CH, Shames BD, Reznikov LL. et al. Liposomal delivery of purified inhibitory-kappaBalpha inhibits tumor necrosis factor-alpha-induced human vascular smooth muscle proliferation. Circ Res 1999; 84: 867-75.
- 24 Watanabe S, Mu W, Kahn A. et al. Role of JAK/ STAT pathway in IL-6-induced activation of vascular smooth muscle cells. AmJ Nephrol 2004; 24: 387-92.
- 25 Stapp JM, Sjoelund V, Lassiter HA. et al. Recombinant rat IL-1beta and IL-6 synergistically enhance C3 mRNA levels and complement component C3 secretion by H-35 rat hepatoma cells. Cytokine 2005; 30: 78-85.
- 26 Berge V, Johnson E, Berge KE. Interleukin-1 alpha, interleukin 6 and tumor necrosis factor alpha increase the synthesis and expression of the functional alternative and terminal complement pathways by human umbilical vein endothelial cells in vitro. Apmis 1996; 104: 213-9.
- 27 Buono C, Come CE, Witztum JL. et al. Influence of C3 deficiency on atherosclerosis. Circulation 2002; 105: 3025-31.