Endothelial dysfunction is the earliest marker for age-related abnormalities in vascular function, and examination of endothelial function has important clinical relevance. The present study was performed to evaluate effects of aging on arterial elasticity by using pulse waveform analysis and to investigate whether the changes in arterial elasticity might be used as a noninvasive measure for endothelial dysfunction. A total of 24 healthy male volunteers were divided into young (n = 12) and elderly (n = 12) groups. Endothelial function was evaluated by delivering acetylcholine (Ach) and sodium nitroprusside (SNP) to the forearm vessels using iontophoresis, respectively, and measured blood flow using laser Doppler fluximetry. Large and small artery elasticity indices were noninvasively assessed using pulse wave analysis. Basal blood flow was similar between the young and elderly groups (14.58 +/- 3.4 v 13.52 +/- 3.41 PU, P = NS). Peak blood flow induced by Ach was significantly reduced in the elderly group compared with the young group (83.4 +/- 11.9 v 93.75 +/- 10.87 PU, P < .05). However, peak blood flow induced by SNP was similar in the two groups (119.17 +/- 16.76 v 128.33 +/- 21.29 PU, P = NS). In parallel, C1 large artery elasticity and C2 small artery elasticity indices were significantly reduced in the elderly group compared with the young group (11.42 +/- 1.67 v 16.75 +/- 2.09 mL/mm Hg x 10, P < .001; and 7.67 +/- 1.56 v 10.75 +/- 1.86 mL/mm Hg x 100, P < .001, respectively). The Ach-induced peak blood flow correlated with C1 large and C2 small artery elasticity indices. Advancing age is associated with endothelial dysfunction and reduced arterial elasticity. Reduced arterial elasticity parallels changes in impaired endothelium dependent vasodilation. It appears that reduced arterial elasticity may be used as a noninvasive measure for the determination of endothelial function.

Background: Although some studies show a positive association between periodontitis and blood pressure (BP) elevation, research on the effect of intensive periodontal treatment on decline in BP levels and endothelial microparticles (EMPs) without any antihypertensive management is lacking. Therefore, the present clinical trial explores whether intensive periodontal therapy would lower BP levels and EMPs of patients with prehypertension with periodontitis.Methods: From a total 107 patients, 95 underwent randomization (47 assigned to control‐treatment [CT] group and 48 assigned to intensive‐treatment [IT] group) and completed the trial. Patients received intervention for 4 consecutive weeks and were followed for 6 months. Levels of BP and EMPs were evaluated at baseline and 1, 3, and 6 months after intervention.Results: Periodontal conditions were significantly improved (P <0.05) 6 months after intensive periodontal treatment. In parallel, the primary outcomes including systolic and diastolic BP and EMPs were markedly reduced in the IT group compared with the CT group (absolute difference: 12.57 and 9.65 mm Hg and 581.59/μL, respectively; 95% confidence intervals: 10.45 to 14.69, 7.06 to 12.24, and 348.12 to 815.06, respectively; P <0.05). Reduction in BP levels and EMPs was related to improvement in probing depth (r = 0.358, 0.363, and 0.676, respectively, by the Pearson product‐moment correlation; P = 0.009, 0.008, and P <0.001, respectively).Conclusion: To the best knowledge of the authors, the present study demonstrates for the first time that intensive periodontal intervention without any antihypertensive medication therapy may be an effective means to lower levels of BP and EMPs in patients with prehypertension with periodontitis.

Reduced arterial elasticity is a hallmark of ageing in healthy humans and appears to occur independently of coexisting disease processes. Endothelial-cell injury and dysfunction may be responsible for this fall in arterial elasticity. We hypothesized that circulating endothelial progenitor cells (EPCs) are involved in endothelial repair and that lack of EPCs contributes to impaired arterial elasticity. A total of 56 healthy male volunteers were divided into young (n=26) and elderly (n=30) groups. Large and small artery elasticity indices were noninvasively assessed using pulse wave analysis. The number of circulating EPCs was measured by using flow cytometry. Cells demonstrating DiI-acLDL and FITC-ulex lectin double-positive fluorescence were identified as EPCs. C1 large artery elasticity and C2 small artery elasticity indices were significantly reduced in the elderly group compared with the young group (11.73±1.45 vs 16.88±1.69 ml/mm Hg × 10, P<0.001; 8.40±1.45 vs 10.58±1.18 ml/mm Hg × 100, P<0.001, respectively). In parallel, the number of circulating EPCs was significantly reduced in the elderly group compared with the young group (0.13±0.02 vs 0.17±0.04%, P<0.05). The number of circulating EPCs correlated with C1 large and C2 small artery elasticity indices (r=0.47, P<0.01; r=0.4, P<0.01). The present findings suggest that the fall in circulating EPCs with subsequently impaired endothelial-cell repair and function contributes to reduced arterial elasticity in humans with ageing. The decrease in circulating EPCs may serve as a surrogate biologic measure of vascular function and human age.

Hypertension is characterized by endothelial dysfunction and arterial stiffness, which contribute to the pathogenesis of atherosclerotic cardiovascular diseases. Nicotinamide adenine dinucleotide (NAD⁺) is an indispensable cofactor in all living cells that is involved in fundamental biological processes. However, in hypertensive patients, alterations in NAD⁺ levels and their relation with blood pressure (BP) elevation and vascular damage have not yet been studied. Here we reported that hypertensive patients exhibited lower NAD⁺ levels, as detected by high-performance liquid chromatography-mass spectrometry (HPLC-MS), in both peripheral blood mononuclear cells (PBMCs) and aortas, which was parallel to vascular dysfunction. NAD⁺ boosting therapy with nicotinamide mononucleotide (NMN) supplement reduced BP and ameliorated vascular dysfunction in hypertensive patients (NCT04903210) and AngII-induced hypertensive mice. Upregulation of CD38 in endothelial cells led to endothelial NAD⁺ exhaustion by reducing NMN bioavailability. Pro-inflammatory macrophages infiltration and increase in IL-1β generation derived from pro-inflammatory macrophages resulted in higher CD38 expression by activating JAK1-STAT1 signaling pathway. CD38 KO, CD38 inhibitors treatment, or adeno-associated virus (AAV)-mediated endothelial CD38 knockdown lowered BP and improved vascular dysfunction in AngII-induced hypertensive mice. The present study demonstrated for the first time that endothelial CD38 activation and subsequently accelerated NAD⁺ degradation due to enhanced macrophage-derived IL-1β production was responsible for BP elevation and vascular damage in hypertension. NAD⁺ boosting therapy can be used as a novel therapeutic strategy for the management of hypertensive patients.

Vascular dysfunction in hypertensive condition is characterized by impaired endothelial function and reduced artery elasticity. Circulating endothelial microparticles (EMPs) and brachial–ankle pulse wave velocity (baPWV) are novel evaluation parameters for vascular function. However, their changes in patients with well-controlled blood pressure (BP) have not been fully acquired. To address this issue, circulating EMPs, defined as CD31+/CD42− MPs and baPWV were detected in 30 healthy subjects, 30 uncontrolled hypertensive (UCHT) patients and 23 well-controlled hypertensive (WCHT) patients. UCHT patients displayed elevated baPWV (P<0.01) and circulating EMPs (P<0.01) compared with healthy subjects. In WCHT patients, vascular damage represented by these two parameters constantly existed (P<0.01). Values of circulating EMPs were positively related to baPWV (P<0.01). Multivariate regression defined circulating EMPs as an independent contributor to the increase of baPWV value (P<0.05). Our study indicated that though BP was controlled, impaired endothelial function and arterial elasticity continued. The optimal therapy for patients with hypertension should include not only lowering BP but also improvement of vascular injury in parallel.