Proximal resistance vessels, such as the mesenteric arteries, contribute substantially to the peripheral resistance. The reactivity of resistance vessels to vasoactive substance like natriuretic peptides plays an important role in the regulation of blood pressure. In current study, we investigated the reactivity of mesenteric arteries to atrial natriuretic peptide (ANP), a well known vasodilating factor, in spontaneously hypertensive rats (SHR), as well as the effects of exercise training on it. As a result, ANP-induced vasorelaxation was attenuated in SHR with significantly increased phosphodiesterase type 5 (PDE5), and decreased cGMP/ANP ratio, compared with WKY rats as control. Intriguingly, the decreased reactivity to ANP in SHR was markedly reversed by exercise training. In addition, ANP resistance of in vitro mesenteric arteries was diminished by sildenafil a potent selective inhibitor of PDE5. In conclusion, ANP resistance occurs in resistance vessels of SHR, suggesting predisposition to hypertension, which can be reversed by exercise.

Rationale: Although affecting different arterial territories, the related atherosclerotic vascular diseases coronary artery disease (CAD) and peripheral artery disease (PAD) share similar risk factors and have shared pathobiology. Analysis of their shared genetic architecture, along with that of common risk factors, may identify novel common biology. Objective: To identify novel pleiotropic genetic loci associated with atherosclerosis and provide a better understanding of biological pathways underlying atherosclerosis. Methods and Results: Summary statistics from genome wide association studies (GWAS) of nine known atherosclerotic (CAD, PAD) or atherosclerosis risk factors (body mass index, smoking initiation, type 2 diabetes, low density lipoprotein (LDL), high density lipoprotein, total cholesterol, and triglycerides) were combined to perform 15 separate multi-trait genetic association scans which resulted in 31 unique novel pleiotropic loci not yet reported as genome-wide significant for their respective traits. Colocalization with single-tissue eQTLs identified 34 candidate causal genes across 14 of the detected signals. Notably, the signal between PAD and CAD at the VDAC2 locus (rs7088974) colocalized with VDAC2 expression in aorta and tibial artery tissues. Additionally, the signal between PAD and LDL at the PCSK6 locus (rs1531817) affects PCSK6 splicing in human liver tissue and induced pluripotent derived hepatocyte like cells. Conclusions: Joint analysis of related atherosclerotic disease traits and their risk factors allowed identification of unified biology that may offer the opportunity for therapeutic manipulation. VDAC2 and PCSK6 represent possible shared causal biology where existing inhibitors may be able to be leveraged for novel therapies.

Chiral honeycombs which exhibit auxetic behaviors (negative Poisson's ratios) have attracted much research interest due to their novel mechanical properties. They are broadly used in designing new functional structures, such as energy absorption and noise mitigation materials. To analyze the behaviors of these materials, finite element models are generally adopted, which may require much time and labor to construct and implement. To simplify the numerical modelling, a novel Chiral Beam Element for finite element simulation is proposed in this paper. Both static and dynamic analyses are conducted and the numerical expense, i.e., the modelling procedures and the computational time, is reduced significantly when compared to traditional finite element models.