Mechanisms and Subclinical Consequences of Aortic Stiffness

Pierce, Gary L.

doi:10.1161/hypertensionaha.117.08933

Cited by 25 publications

(29 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A number of clinical studies support the existence of relationships between increased aortic stiffness, albuminuria, and kidney injury [ 7 – 9 , 48 ]. However, the mechanisms behind these interactions are not well understood.…”

Section: Discussionmentioning

confidence: 99%

Glycemic control by the SGLT2 inhibitor empagliflozin decreases aortic stiffness, renal resistivity index and kidney injury

Aroor

Das

Carpenter

et al. 2018

Cardiovasc Diabetol

124

View full text Add to dashboard Cite

BackgroundArterial stiffness is emerging as an independent risk factor for the development of chronic kidney disease. The sodium glucose co-transporter 2 (SGLT2) inhibitors, which lower serum glucose by inhibiting SGLT2-mediated glucose reabsorption in renal proximal tubules, have shown promise in reducing arterial stiffness and the risk of cardiovascular and kidney disease in individuals with type 2 diabetes mellitus. Since hyperglycemia contributes to arterial stiffness, we hypothesized that the SGLT2 inhibitor empagliflozin (EMPA) would improve endothelial function, reduce aortic stiffness, and attenuate kidney disease by lowering hyperglycemia in type 2 diabetic female mice (db/db).Materials/methodsTen-week-old female wild-type control (C57BLKS/J) and db/db (BKS.Cg-Dock7m+/+Leprdb/J) mice were divided into three groups: lean untreated controls (CkC, n = 17), untreated db/db (DbC, n = 19) and EMPA-treated db/db mice (DbE, n = 19). EMPA was mixed with normal mouse chow at a concentration to deliver 10 mg kg−1 day−1, and fed for 5 weeks, initiated at 11 weeks of age.ResultsCompared to CkC, DbC showed increased glucose levels, blood pressure, aortic and endothelial cell stiffness, and impaired endothelium-dependent vasorelaxation. Furthermore, DbC exhibited impaired activation of endothelial nitric oxide synthase, increased renal resistivity and pulsatility indexes, enhanced renal expression of advanced glycation end products, and periarterial and tubulointerstitial fibrosis. EMPA promoted glycosuria and blunted these vascular and renal impairments, without affecting increases in blood pressure. In addition, expression of “reversion inducing cysteine rich protein with Kazal motifs” (RECK), an anti-fibrotic mediator, was significantly suppressed in DbC kidneys and partially restored by EMPA. Confirming the in vivo data, EMPA reversed high glucose-induced RECK suppression in human proximal tubule cells.ConclusionsEmpagliflozin ameliorates kidney injury in type 2 diabetic female mice by promoting glycosuria, and possibly by reducing systemic and renal artery stiffness, and reversing RECK suppression.

show abstract

Section: Discussionmentioning

confidence: 99%

Glycemic control by the SGLT2 inhibitor empagliflozin decreases aortic stiffness, renal resistivity index and kidney injury

Aroor

Das

Carpenter

et al. 2018

Cardiovasc Diabetol

124

View full text Add to dashboard Cite

show abstract

“…Arterial stiffness, an important material property of the arterial wall, is of increasing interest for several reasons . It has been shown to predict cardiovascular disease (CVD) beyond traditional risk factors .…”

Section: Introductionmentioning

confidence: 99%

Cardio‐ankle vascular index and cardiovascular disease: Systematic review and meta‐analysis of prospective and cross‐sectional studies

Matsushita

Kim

Budoff

et al. 2018

J of Clinical Hypertension

View full text Add to dashboard Cite

The cardio‐ankle vascular index (CAVI) is a new measure of arterial stiffness that reflects the stiffness from the ascending aorta to the ankle arteries, and demonstrates little dependence on blood pressure during the evaluation. However, a comprehensive assessment of the association of CAVI with cardiovascular disease (CVD) has not been reported. We performed a systematic review to assess the association between CAVI and CVD. We searched for both prospective and cross‐sectional studies using MEDLINE, Embase, and Cochrane from inception until April 11, 2017. We pooled the results using random‐effects models. Among 1519 records, we identified nine prospective studies (n = 5214) and 17 cross‐sectional eligible studies (n = 7309), with most enrolling high CVD risk populations in Asia. All nine prospective studies investigated composite CVD events as an outcome (498 cases including coronary events and stroke) but modeled CAVI inconsistently. The pooled adjusted hazard ratio for CVD events per 1 standard deviation increment of CAVI in four studies was 1.20 (95% CI: 1.05‐1.36, P = 0.006). Of the 17 cross‐sectional studies, 13 studies compared CAVI values between patients with and without CVD and all reported significantly higher values in those with CVD (pooled mean difference in CAVI values 1.28 [0.86‐1.70], P < 0.001). This systematic review suggests a modest association between CAVI and incident CVD risk, and highlights the need for studies assessing CAVI as a predictor of CVD in the general population and non‐Asian countries.

show abstract

“…The cardioprotective effects of klotho have been recently reported [ 183 ]. Among the downstream targets of klotho, Sirt1 and AMPK are considered to be CV protective molecules [ 184 ]. Importantly, aging is associated with a decrease in circulating klotho levels [ 185 ].…”

Section: Introductionmentioning

confidence: 99%

The role of dipeptidylpeptidase-4 inhibitors in management of cardiovascular disease in diabetes; focus on linagliptin

Aroor

Manrique‐Acevedo

DeMarco

2018

Cardiovasc Diabetol

View full text Add to dashboard Cite

Multiple population based analyses have demonstrated a high incidence of cardiovascular disease (CVD) and cardiovascular (CV) mortality in subjects with T2DM that reduces life expectancy by as much as 15 years. Importantly, the CV system is particularly sensitive to the metabolic and immune derangements present in obese pre-diabetic and diabetic individuals; consequently, CV dysfunction is often the initial CV derangement to occur and promotes the progression to end organ/tissue damage in T2DM. Specifically, diabetic CVD can manifest as microvascular complications, such as nephropathy, retinopathy, and neuropathy, as well as, macrovascular impairments, including ischemic heart disease, peripheral vascular disease, and cerebrovascular disease. Despite some progress in prevention and treatment of CVD, mainly via blood pressure and dyslipidemia control strategies, the impact of metabolic disease on CV outcomes is still a major challenge and persists in proportion to the epidemics of obesity and diabetes. There is abundant pre-clinical and clinical evidence implicating the DPP-4-incretin axis in CVD. In this regard, linagliptin is a unique DPP-4 inhibitor with both CV and renal safety profiles. Moreover, it exerts beneficial CV effects beyond glycemic control and beyond class effects. Linagliptin is protective for both macrovascular and microvascular complications of diabetes in preclinical models, as well as clinical models. Given the role of endothelial-immune cell interactions as one of the key events in the initiation and progression of CVD, linagliptin modulates these cell–cell interactions by affecting two important pathways involving stimulation of NO signaling and potent inhibition of a key immunoregulatory molecule.

show abstract

Mechanisms and Subclinical Consequences of Aortic Stiffness

Cited by 25 publications

References 55 publications

Glycemic control by the SGLT2 inhibitor empagliflozin decreases aortic stiffness, renal resistivity index and kidney injury

Glycemic control by the SGLT2 inhibitor empagliflozin decreases aortic stiffness, renal resistivity index and kidney injury

Cardio‐ankle vascular index and cardiovascular disease: Systematic review and meta‐analysis of prospective and cross‐sectional studies

The role of dipeptidylpeptidase-4 inhibitors in management of cardiovascular disease in diabetes; focus on linagliptin

Contact Info

Product

Resources

About