Associations among oxidative stress, Lp-PLA 2 activity and arterial stiffness according to blood pressure status at a 3.5-year follow-up in subjects with prehypertension

Kim, Minkyung; Yoo, Hye Jin; Ahn, Hyeon Yeong; Park, Jiyeong; Lee, Sang Hyun; Lee, Jong Ho

doi:10.1016/j.atherosclerosis.2017.01.006

Cited by 18 publications

(19 citation statements)

References 28 publications

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“…All systems were simulated with a 2 fs time-step with NAMD version 2.9 53 . Long-range electrostatics was obtained by using the particle-mesh Ewald (PME) method 54 with an interpolation order of 6 and a direct space tolerance of 6 – 10 . The van der Waals interaction was switched off from 10 to 12 Å by the force-based switching function 55 .…”

Section: Methodsmentioning

confidence: 99%

“…Lysophospholipids as surfactants can further damage membranes by solubilizing them. Lipoprotein associated PLA2 contributes to oxidative stress, thus increasing the hydrolysis of low-density lipoprotein (LDL) resulting in increased endothelial dysfunction and stiffness 10 . Therefore, people with a high concentration of lipoprotein associated PLA2 are at high risk of cardiovascular disease and stroke 11 .…”

Section: Introductionmentioning

confidence: 99%

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Molecular Mechanism of Resveratrol’s Lipid Membrane Protection

Fei

Kent

Botello‐Smith

et al. 2018

Sci Rep

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Resveratrol, a natural compound found in red wine and various vegetables, has drawn increasing interest due to its reported benefit in cardiovascular protection, neurodegenerative disorders, and cancer therapy. The mechanism by which resveratrol exerts such pleiotropic effects remains unclear. It remains as one of the most discussed polyphenol compounds in the debating "French Paradox". In this study, using molecular dynamics simulations of dipalmitoyl phosphatidylcholine (DPPC) bilayer with resveratrol, we generated a free energy map of resveratrol’s location and orientation of inside the lipid bilayer. We found that resveratrol increases the surface area per lipid and decreases membrane thickness, which is the opposite effect of the well-studied cholesterol on liquid phase DPPC. Most importantly, based on the simulation observation that resveratrol has a high probability of forming hydrogen bonds with sn-1 and sn-2 ester groups, we discovered a new mechanism using experimental approach, in which resveratrol protects both sn-1 and sn-2 ester bonds of DPPC and distearoyl phosphatidylcholine (DSPC) from phospholipase A1 (PLA1) and phospholipase A2 (PLA2) cleavage. Our study elucidates the new molecular mechanism of potential health benefits of resveratrol and possibly other similar polyphenols and provides a new paradigm for drug design based on resveratrol and its analogs.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Molecular Mechanism of Resveratrol’s Lipid Membrane Protection

Fei

Kent

Botello‐Smith

et al. 2018

Sci Rep

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“…In a recent longitudinal study, Kim et al. () observed significant increases in circulating Lp‐PLA2 activity after 3.5 years in individuals with persistent prehypertension compared to individuals whose BP status reverted to normotension, suggesting that vascular inflammation is associated with the maintenance of elevated resting BP. Alongside increases in Lp‐PLA2, E‐selectin was higher and ICAM‐1 tended to be higher in ERBP.…”

Section: Discussionmentioning

confidence: 99%

“…; Kim et al. ), and shown in longitudinal studies to be a reliable predictor of cardiovascular events (Madjid et al. ).…”

Section: Discussionmentioning

confidence: 99%

“…Second, we measured systemic biomarkers of inflammation rather than directly from blood vessels; however, Lp‐PLA2, E‐selectin, and ICAM have been shown to reflect vascular inflammation in prior studies (Krieglstein and Granger ; Kim et al. ). Third, 25% of the variance in increasing MSNA is explained by E‐selectin, and 23% of the variance in increasing MSNA is explained by changes in ICAM‐1.…”

Section: Discussionmentioning

confidence: 99%

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Sympathoexcitation and impaired arterial baroreflex sensitivity are linked to vascular inflammation in individuals with elevated resting blood pressure

Fonkoue

Kankam

et al. 2019

Physiol Rep

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Elevated Resting Blood Pressure ( ERBP ) in the prehypertensive range is associated with increased risk of hypertension and cardiovascular disease, the mechanisms of which remain unclear. Prior studies have suggested that ERBP may be associated with overactivation and dysregulation of the sympathetic nervous system ( SNS ). We hypothesized that compared to normotensives (≤120/80 mmHg), ERBP (120/80–139/89 mmHg) has higher SNS activity, impaired arterial baroreflex sensitivity ( BRS ), and increased vascular inflammation. Twenty‐nine participants were studied: 16 otherwise healthy individuals with ERBP (blood pressure ( BP ) 130 ± 2/85 ± 2 mmHg) and 13 matched normotensive controls (mean BP 114 ± 2/73 ± 2 mmHg). We measured muscle sympathetic nerve activity ( MSNA ), beat‐to‐beat BP , and continuous electrocardiogram at rest and during arterial BRS testing via the modified Oxford technique. Blood was analyzed for the following biomarkers of vascular inflammation: lipoprotein‐associated phospholipase A2 (Lp‐ PLA 2), E‐selectin, and intercellular adhesion molecule 1 ( ICAM ‐1). Resting MSNA burst frequency (22 ± 2 vs. 16 ± 2 bursts/min, P = 0.036) and burst incidence (36 ± 3 vs. 25 ± 3 bursts/100 heart beats, P = 0.025) were higher in ERBP compared to controls. Cardiovagal BRS was blunted in ERBP compared to controls (13 ± 2 vs. 20 ± 3 msec/mmHg, P = 0.032), while there was no difference in sympathetic BRS between groups. Lp‐ PLA 2 (169 ± 8 vs. 142 ± 9 nmol/min/ mL , P = 0.020) and E‐selectin (6.89 ± 0.6 vs. 4.45 ± 0.51 ng/ mL , P = 0.004) were higher in ERBP versus controls. E‐selectin ( r = 0.501, P = 0.011) and ICAM ‐1 ( r = 0.481, P = 0.015) were positively correlated with MSNA , while E‐selectin was negatively correlated with cardiovagal BRS ( r = −0.427, P = 0.030). These findings demonstrate that individuals with ERBP have SNS overactivity and impaired arterial BRS that are linked to biomarkers of vascular inflammation.

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Arterial Stiffness in Early Phases of Prehypertension

Laurent

Cunha

2018

Updates in Hypertension and Cardiovascular Protection

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Children, adolescent, and adults with prehypertension have a high risk for developing hypertension. Modifiable cardiovascular risk factors, such as prediabetes and diabetes mellitus, overweight and obesity, high lipid diet, high salt intake, and lack of regular physical activity play a crucial role in the transition between prehypertension and hypertension. Because these cardiovascular risk factors are key determinants of increased arterial stiffness, and because increased arterial stiffness is a determinant of incident hypertension, the question arises as to whether arterial stiffness plays a crucial role in the transition between early phases of prehypertension and hypertension. In this review, we will analyze the epidemiological and hemodynamic evidences that increased arterial stiffness is a determinant of incident hypertension. We will also address the complexity of this relationship by discussing the hemodynamic and biomechanical pathways involved in the bidirectional influence between arterial stiffness and blood pressure. And then, we will discuss (a) the predictive value of arterial stiffness not only for incident hypertension, but also for cardiovascular events, (b) the influence of low-grade inflammation associated with chronic diseases in the development of arterial stiffness and subsequently hypertension, (c) how the concept of Early Vascular Ageing can help understanding the relationship between arterial stiffness and prehypertension, and (d) the relationships between metabolic syndrome, arterial stiffness, and prehypertension in children.

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Associations among oxidative stress, Lp-PLA 2 activity and arterial stiffness according to blood pressure status at a 3.5-year follow-up in subjects with prehypertension

Cited by 18 publications

References 28 publications

Molecular Mechanism of Resveratrol’s Lipid Membrane Protection

Molecular Mechanism of Resveratrol’s Lipid Membrane Protection

Sympathoexcitation and impaired arterial baroreflex sensitivity are linked to vascular inflammation in individuals with elevated resting blood pressure

Arterial Stiffness in Early Phases of Prehypertension

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