FIGURE 1.

Pharmacologic inhibition of HDAC6 attenuates elevated vascular stiffness and protects impaired endothelial-dependent vascular relaxation in atherogenic mice. Six- to eight-week-old C57BL/6 mice were injected with adeno-associated virus (AAV) encoding a PCSK9 gain-of-function mutant and then were fed a high-fat diet (HFD) for 18 weeks in the presence or absence of the HDAC6 inhibitor tubacin (0.5 mg/kg daily). (A) Pulse wave velocity (PWV) and (B) body weight was measured every 2 weeks until the end of the diet regimen (18 weeks). ^∗p < 0.05 vs. vehicle group; n = 10–12. Vascular reactivity in response to (C) acetylcholine and (D) sodium nitroprusside (SNP) was measured by wire myography of isolated aortic rings. ^∗p < 0.05 vs. control group; n = 6–8 mice. (E) Oil Red O staining was used to determine plaque burden in isolated aortas. (F) Quantification of plaque area presented in (E). ^∗∗p < 0.05 vs. normal diet group; ^#p < 0.05 vs. PCSK9aav + HFD group; n = 3. (G) Frozen aortic root cross sections were stained with Oil Red O. The graph in the lower right quadrant shows quantification of plaque area. ^∗p < 0.05 vs. normal diet group; ^#p < 0.05 vs. PCSK9aav + HFD group; n = 3.