Arterial stiffness is an age-related disorder. In the medial layer of arteries, mechanical fracture due to fatigue failure for the pulsatile wall strain causes medial degeneration vascular remodeling. The alteration of extracellular matrix composition and arterial geometry result in structural arterial stiffness. Calcium deposition and other factors such as advanced glycation end product-mediated collagen cross-linking aggravate the structural arterial stiffness. On the other hand, endothelial dysfunction is a cause of arterial stiffness. The biological molecular mechanisms relating to aging are known to involve the progression of arterial stiffness. Arterial stiffness further applies stress on large arteries and also microcirculation. Therefore, it is closely related to adverse outcomes in cardiovascular and cerebrovascular system. Cardio-ankle vascular index (CAVI) is a promising diagnostic tool for evaluating arterial stiffness. The principle is based on stiffness parameter β, which is an index intended to assess the distensibility of carotid artery. Stiffness parameter β is a two-dimensional technique obtained from changes of arterial diameter by pulse in one section. CAVI applied the stiffness parameter β to all of the arterial segments between heart and ankle using pulse wave velocity. CAVI has been commercially available for a decade and the clinical data of its effectiveness has accumulated. The characteristics of CAVI differ from other physiological tests of arterial stiffness due to the independency from blood pressure at the time of examination. This review describes the pathophysiology of arterial stiffness and CAVI. Molecular mechanisms will also be covered.

Metabolic syndrome (Mets) is the major contributor to the onset of metabolic complications, such as hypertension, type 2 diabetes mellitus (DM), dyslipidemia, and non-alcoholic fatty liver disease, resulting in cardiovascular diseases. C57BL/6 mice on a high-fat and high-sucrose diet (HFHSD) are a well-established model of Mets but have minor endothelial dysfunction in isolated aortas without perivascular adipose tissue (PVAT). The purpose of this study was to evaluate the effects of additional factors such as DM, dyslipidemia, and steatohepatitis on endothelial dysfunction in aortas without PVAT. Here, we employed eight-week-old male C57BL/6 mice fed with a normal diet (ND), HFHSD, steatohepatitis choline-deficient HFHSD (HFHSD-SH), and HFHSD containing 1% cholesterol and 0.1% deoxycholic acid (HFHSD-Chol) for 16 weeks. At week 20, some HFHSD-fed mice were treated with streptozocin to develop diabetes (HFHSD-DM). In PVAT-free aortas, the endothelial-dependent relaxation (EDR) did not differ between ND and HFHSD (p = 0.25), but in aortas with PVAT, the EDR of HFHSD-fed mice was impaired compared with ND-fed mice (p = 0.005). HFHSD-DM, HFHSD-SH, and HFHSD-Chol impaired the EDR in aortas without PVAT (p < 0.001, p = 0.019, and p = 0.009 vs. ND, respectively). Furthermore, tempol rescued the EDR in those models. In the Mets model, the EDR is compromised by PVAT, but with the addition of DM, dyslipidemia, and SH, the vessels themselves may result in impaired EDR.