Cardiovascular risk factors and molecular routes underlying endothelial dysfunction: Novel opportunities for primary prevention

Benincasa, Giuditta; Coscioni, Enrico; Napoli, Claudio

doi:10.1016/j.bcp.2022.115108

Cited by 48 publications

(48 citation statements)

References 159 publications

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“…Endothelial dysfunction, the impaired endothelium-dependent dilation of blood vessels, is considered to be both a cardiovascular disease marker and a pathogenetic factor contributing to the development and progression of cardio- and cerebrovascular disease, including stroke [ 34 , 35 ]. Endothelial dysfunction is caused by impaired basal and stimulated release and activity of nitric oxide (NO) that functions as a powerful vasodilator, an inhibitor of platelet and leukocyte aggregation, and an anti-inflammatory agent [ 36 ]. The contribution of endothelial NO to both maintenance of basal CBF and endothelial-dependent vascular reactivity is traditionally evaluated in both in vivo and in vitro experiments as the dilatory response to Ach, a physiologic stimulator of NO release [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

“…Endothelial dysfunction is caused by impaired basal and stimulated release and activity of nitric oxide (NO) that functions as a powerful vasodilator, an inhibitor of platelet and leukocyte aggregation, and an anti-inflammatory agent [ 36 ]. The contribution of endothelial NO to both maintenance of basal CBF and endothelial-dependent vascular reactivity is traditionally evaluated in both in vivo and in vitro experiments as the dilatory response to Ach, a physiologic stimulator of NO release [ 36 , 37 ]. Importantly, in PSs rats, the endothelial dysfunction was evident as an inverse response to Ach, while in PSr rats, there was no significant response to Ach.…”

Section: Discussionmentioning

confidence: 99%

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Cerebral Blood Flow in Predator Stress-Resilient and -Susceptible Rats and Mechanisms of Resilience

Kondashevskaya

Downey

Tseĭlikman

et al. 2022

IJMS

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Stress-induced conditions are associated with impaired cerebral blood flow (CBF) and increased risk of dementia and stroke. However, these conditions do not develop in resilient humans and animals. Here the effects of predator stress (PS, cat urine scent, ten days) on CBF and mechanisms of CBF regulation were compared in PS-susceptible (PSs) and PS-resilient (PSr) rats. Fourteen days post-stress, the rats were segregated into PSs and PSr groups based on a behavior-related anxiety index (AI). CBF and its endothelium-dependent changes were measured in the parietal cortex by laser Doppler flowmetry. The major findings are: (1) PS susceptibility was associated with reduced basal CBF and endothelial dysfunction. In PSr rats, the basal CBF was higher, and endothelial dysfunction was attenuated. (2) CBF was inversely correlated with the AI of PS-exposed rats. (3) Endothelial dysfunction was associated with a decrease in eNOS mRNA in PSs rats compared to the PSr and control rats. (4) Brain dopamine was reduced in PSs rats and increased in PSr rats. (5) Plasma corticosterone of PSs was reduced compared to PSr and control rats. (6) A hypercoagulation state was present in PSs rats but not in PSr rats. Thus, potential stress resilience mechanisms that are protective for CBF were identified.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cerebral Blood Flow in Predator Stress-Resilient and -Susceptible Rats and Mechanisms of Resilience

Kondashevskaya

Downey

Tseĭlikman

et al. 2022

IJMS

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“…This decision was made after extensive consideration and reflects the variability in the literature and outcomes associated with different models of disease risk. While there is evidence that vasoconstrictor responses to an exogenous challenge can be impacted by chronic disease risk conditions ( Stapleton et al, 2008 ; Lemaster et al, 2017b ), it is far from a consensus opinion and can be extremely model-dependent, especially when compared to the monumental amount of previous evidence demonstrating the impairment to dilator reactivity in both the cerebral and skeletal muscle circulations that are well correlated with outcome risk severity ( Stapleton et al, 2008 ; Benincasa et al, 2022 ; Zhang, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

A novel vascular health index: Using data analytics and population health to facilitate mechanistic modeling of microvascular status

Menon

Halvorson²,

Alimorad³

et al. 2022

Front. Physiol.

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The study of vascular function across conditions has been an intensive area of investigation for many years. While these efforts have revealed many factors contributing to vascular health, challenges remain for integrating results across research groups, animal models, and experimental conditions to understand integrated vascular function. As such, the insights attained in clinical/population research from linking datasets, have not been fully realized in the basic sciences, thus frustrating advanced analytics and complex modeling. To achieve comparable advances, we must address the conceptual challenge of defining/measuring integrated vascular function and the technical challenge of combining data across conditions, models, and groups. Here, we describe an approach to establish and validate a composite metric of vascular function by comparing parameters of vascular function in metabolic disease (the obese Zucker rat) to the same parameters in age-matched, “healthy” conditions, resulting in a common outcome measure which we term the vascular health index (VHI). VHI allows for the integration of datasets, thus expanding sample size and permitting advanced modeling to gain insight into the development of peripheral and cerebral vascular dysfunction. Markers of vascular reactivity, vascular wall mechanics, and microvascular network density are integrated in the VHI. We provide a detailed presentation of the development of the VHI and provide multiple measures to assess face, content, criterion, and discriminant validity of the metric. Our results demonstrate how the VHI captures multiple indices of dysfunction in the skeletal muscle and cerebral vasculature with metabolic disease and provide context for an integrated understanding of vascular health under challenged conditions.

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“…Since previous FMD studies have reported differences regarding their adherence to key methodological issues, we have overcome this problem by means of a well-defined analysis protocol [ 18 ]. FMD is reduced in subjects with atherosclerosis and cardiovascular risk factors—smokers [ 19 ], subjects with high cholesterol levels [ 20 ], arterial hypertension [ 21 ], diabetes [ 22 ], obesity, aging [ 23 ], and renal failure [ 24 ]. Endothelial dysfunction measured by the FMD of the brachial artery has already been proven in patients with PAPS and SLE [ 25 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

Asymmetric Dimethylarginine Is a Marker of Endothelial Dysfunction in Thrombotic Antiphospholipid Syndrome Patients

Stanisavljević

Stojanovich

Djoković

et al. 2022

IJMS

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Objective: The potential contribution of asymmetric dimethylarginine (ADMA) and high-sensitivity C reactive protein (hsCRP) to endothelial dysfunction in APS patients has not been studied in detail, until now. The study involved 105 APS patients (59 diagnosed with primary APS (PAPS) and 46 APS associated with systemic lupus erythematosus (SAPS)) who were compared to 40 controls. Endothelial dysfunction was assessed by measurement of flow-mediated dilatation (FMD) and glyceryl trinitrate dilatation (NMD) of the brachial artery. ADMA (micromol/L) was analyzed by ELISA. Results: FMD in patients with APS was significantly lower than that of the controls (p < 0.001), with no difference between the PAPS and the SAPS groups. ADMA and hsCRP concentrations were significantly higher in the patient cohort than in the control group (p < 0.001, p = 0.006, respectively), as was the case with the SAPS group as compared to the PAPS group (p < 0.001, p = 0.022, respectively). FMD impairment correlated to ADMA (ρ 0.472, p < 0.001) and to hsCRP (ρ 0.181, p = 0.033). In the regression model, the ADMA concentration confirmed the strength of its association (B 0.518, SE 0.183, Wald 8.041, p = 0.005, Exp(B) 1.679, 95% CI 1.174–2.402) to FMD impairment. The synergistic probability model of ADMA and hsCRP caused FMD impairment when the positivity of β2GPIIgG was added. ADMA may be used as a simple and low-cost tool for verifying the presence of endothelial dysfunction in APS patients. According to the results of the study, we could presume that hsCRP, together with aPL, has a preparatory effect on the endothelium in causing endothelial dysfunction.

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Cardiovascular risk factors and molecular routes underlying endothelial dysfunction: Novel opportunities for primary prevention

Cited by 48 publications

References 159 publications

Cerebral Blood Flow in Predator Stress-Resilient and -Susceptible Rats and Mechanisms of Resilience

Cerebral Blood Flow in Predator Stress-Resilient and -Susceptible Rats and Mechanisms of Resilience

A novel vascular health index: Using data analytics and population health to facilitate mechanistic modeling of microvascular status

Asymmetric Dimethylarginine Is a Marker of Endothelial Dysfunction in Thrombotic Antiphospholipid Syndrome Patients

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