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- 저자 : Deniz Yeter (검색결과 1 건)
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Deniz Yeter,Richard Deth,Ho-Chang Kuo 대한심장학회 2013 Korean Circulation Journal Vol.43 No.9
Previously, we reviewed biological evidence that mercury could induce autoimmunity and coronary arterial wall relaxation as observed in Kawasaki syndrome (KS) through its effects on calcium signaling, and that inositol 1,4,5-triphosphate 3-kinase C (ITPKC) susceptibility in KS would predispose patients to mercury by increasing Ca 2+ release. Hg 2+ sensitizes inositol 1,4,5-triphosphate (IP3) receptors at low doses, which release Ca 2+ from intracellular stores in the sarcoplasmic reticulum, resulting in delayed, repetitive calcium influx. ITPKC prevents IP3from triggering IP3 receptors to release calcium by converting IP3 to inositol 1,3,4,5-tetrakisphosphate. Defective IP3 phosphorylation re-sulting from reduced genetic expressions of ITPKC in KS would promote IP3, which increases Ca 2+ release. Hg 2+ increases catecholamine levels through the inhibition of S-adenosylmethionine and subsequently catechol-O-methyltransferase (COMT), while a single nucleotide polymorphism of the COMT gene (rs769224) was recently found to be significantly associated with the development of coronary artery le -sions in KS. Accumulation of norepinephrine or epinephrine would potentiate Hg 2+ -induced calcium influx by increasing IP3 production and increasing the permeability of cardiac sarcolemma to Ca 2+ . Norepinephrine and epinephrine also promote the secretion of atrial natri-uretic peptide, a potent vasodilator that suppresses the release of vasoconstrictors. Elevated catecholamine levels can induce hypertension and tachycardia, while increased arterial pressure and a rapid heart rate would promote arterial vasodilation and subsequent fatal throm-boses, particularly in tandem. Genetic risk factors may explain why only a susceptible subset of children develops KS although mercury ex-posure from methylmercury in fish or thimerosal in pediatric vaccines is nearly ubiquitous. During the infantile acrodynia epidemic, only 1in 500 children developed acrodynia whereas mercury exposure was very common due to the use of teething powders. This hypothesis mirrors the leading theory for KS in which a widespread infection only induces KS in susceptible children. Acrodynia can mimic the clinical picture of KS, leading to its inclusion in the differential diagnosis for KS. Catecholamine levels are often elevated in acrodynia and may also play a role in KS. We conclude that KS may be the acute febrile form of acrodynia.
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