Do high-density lipoprotein cholesterol and apolipoprotein A1 levels strongly influence the reactivity of small peripheral arteries?
HDL cholesterol and apolipoprotein A1 levels had a strong, positive correlation with small artery reactive hyperaemia, whereas smoking, waist circumference and triglyceride levels were inversely associated. HDL cholesterol was the main determinant of RHI in small peripheral resistance arteries.
The results identify intracellular folding defects as a novel mechanism of SPINK1 deficiency associated with chronic pancreatitis. The dramatic effects of the D50E and Y54H mutations indicate that the interaction between Asp50 and Tyr54 is critical for proper folding of the inhibitor. The disease-causing biochemical defect in the N34S mutant is unrelated to secretion or trypsin inhibitory activity and remains enigmatic. Finally, the patent functional defects in mutants D50E, Y54H, and R67C suggest disease association of these rare SPINK variants.