Disease relevance of CACNB2

• CAB-2 also blocks the activation of complement in vivo, inhibiting both the Arthus reaction and Forssman shock in guinea pigs [1].

High impact information on CACNB2

• The gene product is a soluble, glycosylated, 110-kDa protein named complement activation blocker-2 (CAB-2) [1].
• Studies in rats demonstrate CAB-2 to exhibit favorable biphasic pharmacokinetics with a t1/2 alpha of 10 min and a t1/2 beta of 8 h; the beta phase accounts for 93% of the administered dose [1].
• The complement activity of the perfusate was reduced by CAB-2, as was the generation of C3a and SC5b-9 [2].
• The myocardial tissues had similar deposition of IgG, IgM, and Clq; however, CAB-2 reduced the deposition of C3, C4, and C9 [2].
• CAB-2 also retarded the onset of increased coronary vascular resistance [2].

Biological context of CACNB2

• Genetic and heterologous expression studies revealed loss-of-function missense mutations in CACNA1C (A39V and G490R) and CACNB2 (S481L) encoding the alpha1- and beta2b-subunits of the L-type calcium channel [3].
• CAB-2 may be an effective therapeutic treatment of acute human diseases in which excessive complement activation causes damage to normal tissues [1].
• Ex vivo, addition of CAB-2 to human blood prolonged organ survival from 17.3 +/- 6.4 min in controls to 108 +/- 55.6 min with 910 nM (100 microg/ml) CAB-2 and 219.8 +/- 62.7 min with 1820 nM (200 microg/ml) CAB-2 [2].
• The two monkeys given multiple doses of CAB-2 had graft survivals of 95 and 96 h [4].

Anatomical context of CACNB2

• RESULTS: In vitro, addition of CAB-2 to serum inhibited cytotoxicity and the deposition of C4b and iC3b on the endothelial cells [2].

Analytical, diagnostic and therapeutic context of CACNB2

• CONCLUSION: These results indicate that CAB-2 can function as an inhibitor of complement activation and markedly reduce tissue injury in models of pig-to-human xenotransplantation and thus may represent a useful therapeutic agent for xenotransplantation and other complement-mediated conditions [2].
• Therefore, we studied the efficacy of CAB-2 when a pig heart is transplanted heterotopically into rhesus monkeys receiving no immunosuppression [4].

References