Active Low-Carber Forums - Beating down LDL

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4298671/

Quote:

PCSK9 and LDLR are also expressed in ß-cells. PCSK9-knockout mice carry more LDLR and less insulin in the pancreas, leading to hyperglycemia and glucose intolerance. ß-cell islets of PCSK9-knockout mice inhibit signs of inflammation and apoptosis [112]. This phenotype is modulated by gender and age [111]. Glucose tolerance is one of the parameters that will be carefully monitored in the outcome trials with PCSK9 inhibitors, so far the phase II data do not suggest the presence of this potential off-target effect in humans.

Quote:

CSK9 and innate immune response

Pathogen-associated lipids such as lipopolysaccharide (LPS) activate innate immune receptors inducing an inflammatory response, e.g. during sepsis. Mammalian lipid transfer proteins bind pathogen lipids. Interstingly, PCSK9 inhibited LPS uptake in human liver cells [171]. Inhibition of PCSK9 improved survival and inflammation in murine sepsis. The PCSK9 effect was abrogated in LDL receptor (LDLR) knockout mice. These data were confirmed in humans with PCSK9 loss-of-function genetic variants and in humans who are homozygous for an LDLR variant that is resistant to PCSK9. These data suggest that inhibition of PCSK9 mediates pathogen lipid clearance via the LDLR regulating systemic inflammatory response.

This is all fine when you don't want a full immune response. Avoiding death from septic shock is good. But what about immune challenges that the body should normally be capable of handling?

That new york times article

Quote:

The group’s chairman, Dr. Robert J. Smith of Brown University, argued for broader availability of the drugs. He said he sees patients in his own practice with out-of-control cholesterol who are at very high risk because, for example, they have already had a heart attack. Two years is a long time for them to wait for clinical trial findings. “I am unwilling to subject patients to that wait,” Dr. Smith said.

Two years is minimal, if you want to see whether the sorts of problems that show up in rodents will show up in humans. Or whether protective effects that show up in rodents will apply to humans, for that matter.