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1.
The role of potassium in atherosclerosis.
Sahranavard, T, Carbone, F, Montecucco, F, Xu, S, Al-Rasadi, K, Jamialahmadi, T, Sahebkar, A
European journal of clinical investigation. 2021;(3):e13454
Abstract
BACKGROUND Atherosclerosis (AS) is a chronic progressive inflammatory condition with a leading prevalence worldwide. Endothelial dysfunction leads to low-density lipoprotein trafficking into subendothelial space and the subsequent form of oxidized LDL (ox-LDL) within intimal layer, perpetuating the vicious cycle of endothelial dysfunction. K+ exerts beneficial effects in vascular wall by reducing LDL oxidization, vascular smooth muscle cells (VSMCs) proliferation, and free radical generation. K+ also modulates vascular tone through a regulatory effect on cell membrane potential. MATERIALS AND METHODS The most relevant papers on the association between 'potassium channels' and 'atherosclerosis' were selected among those deposited on PubMed from 1990 to 2020. RESULTS Here, we provide a short narrative review that elaborates on the role of K+ in atherosclerosis. This review also update the current knowledge about potential pharmacological agents targeting K+ channels with a special focus on pleiotropic activities of agents such as statins, sulfonylureas and dihydropyridines. CONCLUSION In this review, the mechanism of different K+ channels on vascular endothelium will be summarized, mainly focusing on their pathophysiological role in atherosclerosis and potential therapeutic application.
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2.
Diversity of Lipid Function in Atherogenesis: A Focus on Endothelial Mechanobiology.
Kotlyarov, S
International journal of molecular sciences. 2021;(21)
Abstract
Atherosclerosis is one of the most important problems in modern medicine. Its high prevalence and social significance determine the need for a better understanding of the mechanisms of the disease's development and progression. Lipid metabolism and its disorders are one of the key links in the pathogenesis of atherosclerosis. Lipids are involved in many processes, including those related to the mechanoreception of endothelial cells. The multifaceted role of lipids in endothelial mechanobiology and mechanisms of atherogenesis are discussed in this review. Endothelium is involved in ensuring adequate vascular hemodynamics, and changes in blood flow characteristics are detected by endothelial cells and affect their structure and function.
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3.
Interrupting Prolonged Sitting and Endothelial Function in Polycystic Ovary Syndrome.
Taylor, FC, Dunstan, DW, Fletcher, E, Townsend, MK, Larsen, RN, Rickards, K, Maniar, N, Buman, M, Dempsey, PC, Joham, AE, et al
Medicine and science in sports and exercise. 2021;(3):479-486
Abstract
PURPOSE In healthy adults, the impairment of vascular function associated with prolonged sitting can be mitigated with intermittent brief bouts of activity. It is unknown whether these benefits extend to women with polycystic ovary syndrome (PCOS), in whom vascular function is typically impaired and sitting time is high. We examined the acute effect of regularly interrupting sitting time with brief simple resistance activities (SRA) on vascular function in PCOS. METHODS In a randomized crossover trial, 13 physically inactive women with PCOS (18-45 yr) completed two 3.5-h conditions: 1) uninterrupted sitting (SIT) and 2) sitting interrupted by 3-min bouts of SRA every 30 min. Femoral artery flow-mediated dilation (FMD), resting shear rate, and resting blood flow were measured at 0, 1, and 3.5 h. RESULTS Mean resting femoral shear rate, averaged across the 3.5 h, significantly increased in the SRA condition relative to the SIT condition (40.1 ± 6.1 vs 62.8 ± 6.1 s-1, P < 0.0001). In addition, mean resting blood flow also significantly increased across the 3.5 h for SRA relative to SIT (45.0 ± 9.8 vs 72.8 ± 9.9 mL·min-1, P < 0.0001). There were no differences between conditions in the temporal change in femoral artery FMD across 3.5 h (Ptime-condition > 0.05 for all). CONCLUSION Frequently interrupting sitting with SRA acutely increased resting shear rate and blood flow in women with PCOS but did not alter FMD. With sedentary behavior increasing in prevalence, longer-term studies of similar interventions to reduce and break up sitting time are warranted.
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4.
Body mass-normalized moderate dose of dietary nitrate intake improves endothelial function and walking capacity in patients with peripheral artery disease.
Pekas, EJ, Wooden, TK, Yadav, SK, Park, SY
American journal of physiology. Regulatory, integrative and comparative physiology. 2021;(2):R162-R173
Abstract
Peripheral artery disease (PAD) is characterized by the accumulation of atherosclerotic plaques in the lower extremity conduit arteries, which impairs blood flow and walking capacity. Dietary nitrate has been used to reduce blood pressure (BP) and improve walking capacity in PAD. However, a standardized dose for PAD has not been determined. Therefore, we sought to determine the effects of a body mass-normalized moderate dose of nitrate (0.11 mmol nitrate/kg) as beetroot juice on serum nitrate/nitrite, vascular function, walking capacity, and tissue oxygen utilization capacity in patients with PAD. A total of 11 patients with PAD received either nitrate supplement or placebo in a randomized crossover design. Total serum nitrate/nitrite, resting BP, brachial and popliteal artery endothelial function (flow-mediated dilation, FMD), arterial stiffness (pulse-wave velocity, PWV), augmentation index (AIx), maximal walking distance and time, claudication onset time, and skeletal muscle oxygen utilization were measured pre- and postnitrate and placebo intake. There were significant group × time interactions (P < 0.05) for serum nitrate/nitrite, FMD, BP, walking distance and time, and skeletal muscle oxygen utilization. The nitrate group showed significantly increased serum nitrate/nitrite (Δ1.32 μM), increased brachial and popliteal FMD (Δ1.3% and Δ1.7%, respectively), reduced peripheral and central systolic BP (Δ-4.7 mmHg and Δ-8.2 mmHg, respectively), increased maximal walking distance (Δ92.7 m) and time (Δ56.3 s), and reduced deoxygenated hemoglobin during walking. There were no changes in PWV, AIx, or claudication (P > 0.05). These results indicate that a body-mass normalized moderate dose of nitrate may be effective and safe for reducing BP, improving endothelial function, and improving walking capacity in patients with PAD.
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5.
Menadione-induced endothelial inflammation detected by Raman spectroscopy.
Bik, E, Mateuszuk, L, Stojak, M, Chlopicki, S, Baranska, M, Majzner, K
Biochimica et biophysica acta. Molecular cell research. 2021;(2):118911
Abstract
In this work, the effect of an early oxidative stress on human endothelial cells induced by menadione was studied using a combined methodology of label-free Raman imaging and fluorescence staining. Menadione-induced ROS-dependent endothelial inflammation in human aorta endothelial cells (HAEC) was studied with focus on changes in cytochrome, proteins, nucleic acids and lipids content and their distribution in cells. Fluorescence staining (ICAM-1, VCAM-1, vWF, LipidTox, MitoRos and DCF) was used to confirm endothelial inflammation and ROS generation. The results showed that short time, exposure to menadione did not cause their apoptosis or necrosis (Annexin V Apoptosis Detection Kit) within the 3 h timescale of measurement. On the other hand, 3 h of incubation, did result in endothelial inflammation (ICAM-1, VCAM-1, vWF) that was associated with an increased ROS formation (MitoRos and DCF) suggesting the oxidative stress-mediated inflammation. Chemometric analysis of spectral data enabled the determination of spectroscopic markers of menadione-induced oxidative stress-mediated endothelial inflammation including a decrease of the bands intensity of cytochrome (604, 750, 1128, 1315 and 1585 cm-1), nucleic acids bands (785 cm-1), proteins (1005 cm-1) and increased intensity of lipid bands (722, 1085, 1265, 1303, 1445 and 1660 cm-1), without changes in the spectroscopic signature of the cell nucleus. In conclusion, oxidative stress resulting in endothelial inflammation was featured by significant alterations in the number of biochemical changes in mitochondria and other cellular compartments detected by Raman spectroscopy. Most of these, coexisted with results from fluorescence imaging, and most importantly occurred earlier than the detection of increased ROS or markers of endothelial inflammation.
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6.
Endothelial Dysfunction and Its Clinical Implications.
Poredos, P, Poredos, AV, Gregoric, I
Angiology. 2021;(7):604-615
Abstract
Endothelial dysfunction (ED) plays a substantial role in the pathogenesis of atherosclerosis and some other vascular diseases. ED has been demonstrated in patients with hypercholesterolemia, diabetes, smoking, hypertension, and in patients with atherosclerotic disease. Besides classical risk factors, ED is affected by chronic inflammatory diseases and acute infections, particularly viral diseases. Causes of ED include oxidative stress, inflammation, and shear stress, which decrease the bioavailability of nitric oxide. Markers of ED have been sought, particularly circulating markers. Using these tests, it is possible to evaluate the response to harmful effects of risk factors and the effects of treatment on vessel wall function. Endothelial dysfunction is significantly and directly correlated with the occurrence of cardiac events and the risk of cardiac events increase as ED worsens. Because endothelial function plays a central role in atherogenesis it became a therapeutic target. Endothelial dysfunction is reversible and its improvement may be achieved by elimination of risk factors, inhibitors of endothelium-derived contracting factors (angiotensin-converting enzyme), smoking cessation, lipid-lowering drugs, diet, and physical exercise. By reversing ED, it is possible to restore vascular function.
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7.
The Role of Obesity-Induced Perivascular Adipose Tissue (PVAT) Dysfunction in Vascular Homeostasis.
Stanek, A, Brożyna-Tkaczyk, K, Myśliński, W
Nutrients. 2021;(11)
Abstract
Perivascular adipose tissue (PVAT) is an additional special type of adipose tissue surrounding blood vessels. Under physiological conditions, PVAT plays a significant role in regulation of vascular tone, intravascular thermoregulation, and vascular smooth muscle cell (VSMC) proliferation. PVAT is responsible for releasing adipocytes-derived relaxing factors (ADRF) and perivascular-derived relaxing factors (PDRF), which have anticontractile properties. Obesity induces increased oxidative stress, an inflammatory state, and hypoxia, which contribute to PVAT dysfunction. The exact mechanism of vascular dysfunction in obesity is still not well clarified; however, there are some pathways such as renin-angiotensin-aldosterone system (RAAS) disorders and PVAT-derived factor dysregulation, which are involved in hypertension and endothelial dysfunction development. Physical activity has a beneficial effect on PVAT function among obese patients by reducing the oxidative stress and inflammatory state. Diet, which is the second most beneficial non-invasive strategy in obesity treatment, may have a positive impact on PVAT-derived factors and may restore the balance in their concentration.
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8.
A reconciling hypothesis centred on brain-derived neurotrophic factor to explain neuropsychiatric manifestations in rheumatoid arthritis.
Pedard, M, Quirié, A, Tessier, A, Garnier, P, Totoson, P, Demougeot, C, Marie, C
Rheumatology (Oxford, England). 2021;(4):1608-1619
Abstract
Rheumatoid arthritis (RA) is an autoimmune chronic inflammatory disease characterized by synovitis leading to joint destruction, pain and disability. Despite efficient antirheumatic drugs, neuropsychiatric troubles including depression and cognitive dysfunction are common in RA but the underlying mechanisms are unclear. However, converging evidence strongly suggests that deficit in brain-derived neurotrophic factor (BDNF) signalling contributes to impaired cognition and depression. Therefore, this review summarizes the current knowledge on BDNF in RA, proposes possible mechanisms linking RA and brain BDNF deficiency including neuroinflammation, cerebral endothelial dysfunction and sedentary behaviour, and discusses neuromuscular electrical stimulation as an attractive therapeutic option.
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9.
Effect of Telemedicine Dietary Intervention for Endothelial Function in Patients with Type 2 Diabetes Mellitus on Mediterranean Diet.
Gudban, N, Yehuda, I, Nasir, W, Soboh, S, Tamir, S, Blum, A
The Israel Medical Association journal : IMAJ. 2021;(2):89-93
Abstract
BACKGROUND Patients with type 2 diabetes mellitus (T2DM) have a high rate of cardiovascular disease (CVD). The Mediterranean diet is preferred for CVD prevention. Endothelial dysfunction is demonstrated early in T2DM. OBJECTIVES To study the effects of dietary intervention of T2DM patients without known CVD on endothelial function and vascular inflammation. METHODS A prospective study enrolled 22 patients with T2DM. Patients were divided randomly into two groups: an intervention group with 12 patients (55 ± 7 years old, 6 women) and a control group with 10 patients (59 ± 10 years old, 5 women). Clinical evaluation included body mass index (BMI) and endothelial function measured by the flow mediated percent change (FMD%). Fasting blood was drawn on entry to the study and 3 months later, measuring C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), total cholesterol, triglycerides, and glycosylated hemoglobin (HbA1C%). The intervention was based on weekly telephone calls by a clinical dietitian for 3 months. RESULTS In the intervention group CRP and ICAM-1 were reduced (from 4.2 ± 3.3 mg/dl to 0.4 ± 0.5 mg/dl, P = 0.01 and from 258.6 ± 98.3 ng/ml to 171.6 ± 47.7 ng/ml, P = 0.004). Endothelial function (FMD%) was improved (from 0.5 ± 8.0% to 9.5 ± 11.5%, P = 0.014). No change was observed in BMI, HbA1C%, total cholesterol, and triglycerides levels in either group. CONCLUSIONS Patients with T2DM on the Mediterranean diet who received a weekly telephone call for 3 months improved their endothelial function with reduction of markers of inflammation.
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10.
Fetal oxygen supply can be improved by an effective cross-talk between fetal erythrocytes and vascular endothelium.
Chakraborty, P, Khamit, A, Hermesz, E
Biochimica et biophysica acta. Molecular basis of disease. 2021;(11):166243
Abstract
In twin/multiple pregnancy, siblings experience an adverse intrauterine environment which forms the major etiological factor leading to pathological conditions. The status of the developing fetus is highly determined by the nitric oxide (NO) level, that facilitates vasodilation which in turn modulates the oxygen and nutrition supply. As the umbilical cord (UC) lacks innervation, activation of the endothelial nitric oxide synthase (NOS3) is fundamental to maintain adequate NO production. Recent ground breaking fact showed that under stress conditions, circulating red blood cells (RBCs) can actively produces NO as a "rescue mechanism". Therefore, this study majorly focused on the molecular mechanisms that affected the redox environment by altering NOS3 activation - both in the UC arteries and vein endothelium and RBCs - that have impacts on developmental parameters, like birth weight. In connection to that, we pursued the communication efficiency between the vessels' endothelium and the circulating RBCs in demand of bioavailable NO. Our results indicated that twinning itself at stage 33-35 weeks, does not reduce the NOS3 level and its phosphorylation status in the cord vessels. However, RBC-NOS3 activation is highly upregulated during this period - providing additional evidence for the active regulatory role of fetal RBCs in the rate of blood flow - and this functional activity highly correlates with the birth weight of the fetuses. Detailed analysis on NOS3 signalling at different time points of gestation could establish a benchmark in understanding of the pathophysiological mechanisms involved in the process of developing neonatal vascular diseases.