Small interfering RNA molecules (siRNAs) are designed to intervene in the pathway of RNA interference (RNAi), a naturally operating mechanism, wherein they bind to a complex within the cell termed the RNA-induced silencing complex (RISC); after binding, the RISC structure in the siRNA-RISC complex is altered, allowing it to cleave specific messenger RNA molecules (mRNAs). The siRNA-RISC complex is catalytic, and thus can cleave multiple copies of the mRNA that it targets; cleaved mRNAs are not translated into proteins, and thus the concentration of the protein targeted by the siRNA design is decreased.The proprotein convertase, PCSK9, is a liver-produced and -secreted serine protease whose binding and action on LDL receptors results in their increased lysosomal degradation in hepatocytes, a consequence of which is an increase in the level of circulating LDL cholesterol (and inhibition of which, the decrease in this level). Studies of PCSK9 genetics supported the conclusion that decreases in circulating LDL cholesterol accomplished in this way would result in "diminished cardiovascular risk... with no apparent negative health consequences", and long term administration of antibodies with short in vivo half-lives, 1-2 times a month, reduced circulating PCSK9 and LDL cholesterol levels, with the result of a "lower incidence of cardiovascular events than placebo".
Tar melanosis is an occupational dermatosis that occurs among tar handlers after several years of exposure, characterized by a severe widespread itching that is soon followed by the appearance of reticular pigmentation, telangiectases, and a shiny appearance of the skin. : 858

See also
Skin lesion


== References ==