Genesis Of Atherosclerosis Research Articles

M2 Macrophage Membrane-Camouflaged Fe3 O4 -Cy7 Nanoparticles with Reduced Immunogenicity for Targeted NIR/MR Imaging of Atherosclerosis.

Atherosclerosis （AS） is the primary reason behind cardiovascular diseases, leading to approximately one-third of global deaths. Developing a novel multi-model probe to detect AS is urgently required. Macrophages are the primary cells from which AS genesis occurs. Utilizing natural macrophage membranes coated on the surface of nanoparticles is an efficient delivery method to target plaque sites. Herein, Fe3 O4 -Cy7 nanoparticles (Fe3 O4 -Cy7 NPs), functionalized using an M2 macrophage membrane and a liposome extruder for Near-infrared fluorescence and Magnetic resonance imaging, are synthesized. These macrophage membrane-coated nanoparticles (Fe3 O4 @M2 NPs) enhance the recognition and uptake using active macrophages. Moreover, they inhibit uptake using inactive macrophages and human coronary artery endothelial cells. The macrophage membrane-coated nanoparticles (Fe3 O4 @M0 NPs, Fe3 O4 @M1 NPs, Fe3 O4 @M2 NPs) can target specific sites depending on the macrophage membrane type and are related to C-C chemofactor receptor type 2 protein content. Moreover, Fe3 O4 @M2 NPs demonstrate excellent biosafety in vivo after injection, showing a significantly higher Fe concentration in the blood than Fe3 O4 -Cy7 NPs. Therefore, Fe3 O4 @M2 NPs effectively retain the physicochemical properties of nanoparticles and depict reduced immunological response in blood circulation. These NPs mainly reveal enhanced targeting imaging capability for atherosclerotic plaque lesions.

Paradoxical mortality differential of HDL cholesterol

High-density lipoprotein (HDL) cholesterol has been known for ages to be cardio-protective due to its defensive action against genesis of atherosclerosis. Increasing the serum HDL cholesterol (HDL-C) as a prospective potential to prevent coronary heart disease could not prove beneficial in human trials that put forward a major concern about the role and functional contribution of HDL-C in human health. Many observational studies indicated that extreme high value of serum HDL-C is often associated with high cardiovascular mortality; therefore could be considered as detrimental for healthy survival. Furthermore, observational and genetic studies revealed a possible link between extreme low serumHDL-C and development of common noncardiovascular diseases such as infectious disease, autoimmune disorder, malignancy, type-2 diabetes, kidney, and pulmonary diseases. This review endeavors to update on the various reasons of mortality observed with extreme values of HDL-C reflected in the recent studies along with the probable role of HDL-C in the pathogenesis of these ailments.

The Role of the Coagulation System in Peripheral Arterial Disease: Interactions with the Arterial Wall and Its Vascular Microenvironment and Implications for Rational Therapies.

Peripheral artery disease (PAD) is a clinical manifestation of atherosclerotic disease with a large-scale impact on the economy and global health. Despite the role played by platelets in the process of atherogenesis being well recognized, evidence has been increasing on the contribution of the coagulation system to the atherosclerosis formation and PAD development, with important repercussions for the therapeutic approach. Histopathological analysis and some clinical studies conducted on atherosclerotic plaques testify to the existence of different types of plaques. Likely, the role of coagulation in each specific type of plaque can be an important determinant in the histopathological composition of atherosclerosis and in its future stability. In this review, we analyze the molecular contribution of inflammation and the coagulation system on PAD pathogenesis, focusing on molecular similarities and differences between atherogenesis in PAD and coronary artery disease (CAD) and discussing the possible implications for current therapeutic strategies and future perspectives accounting for molecular inflammatory and coagulation targets. Understanding the role of cross-talking between coagulation and inflammation in atherosclerosis genesis and progression could help in choosing the right patients for future dual pathway inhibition strategies, where an antiplatelet agent is combined with an anticoagulant, whose role, despite pathophysiological premises and trials' results, is still under debate.

The Role of Hydrogen Sulfide in Plaque Stability.

Atherosclerosis is the greatest contributor to cardiovascular events and is involved in the majority of deaths worldwide. Plaque rapture or erosion precipitates life-threatening thrombi, resulting in the obstruction blood flow to the heart (acute coronary syndrome), brain (ischemic stroke) or low extremities (peripheral vascular diseases). Among these events, major causation dues to the plaque rupture. Although the initiation, procession, and precise time of controlling plaque rupture are unclear, foam cell formation and apoptosis, cell death, extracellular matrix components, protease expression and activity, local inflammation, intraplaque hemorrhage, and calcification contribute to the plaque instability. These alterations tightly associate with the function regulation of intraplaque various cell populations. Hydrogen sulfide (H2S) is gasotransmitter derived from methionine metabolism and exerts a protective role in the genesis of atherosclerosis. Recent progress also showed H2S mediated the plaque stability. In this review, we discuss the progress of endogenous H2S modulation on functions of vascular smooth muscle cells, monocytes/macrophages, and T cells, and the molecular mechanism in plaque stability.

The Role of Fine Particles (PM 2.5) in the Genesis of Atherosclerosis and Myocardial Damage: Emphasis on Clinical and Epidemiological Data, and Pathophysiological Mechanisms.

Due to the fact that atherosclerotic cardiovascular diseases (CVDs) dominate in the structure of morbidity, disability and mortality of the population, the study of the risk factors for the development of atherosclerotic CVDs, as well as the study of the underlying pathogenetic mechanisms thereof, is the most important area of scientific research in modern medicine. Understanding these aspects will allow to improve the set of treatment and preventive measures and activities. One of the important risk factors for the development of atherosclerosis, which has been actively studied recently, is air pollution with fine particulate matter (PM 2.5). According to clinical and epidemiological data, the level of air pollution with PM 2.5 exceeds the normative indicators in most regions of the world and is associated with subclinical markers of atherosclerosis and mortality from atherosclerotic CVDs. The aim of this article is to systematize and discuss in detail the role of PM 2.5 in the development of atherosclerosis and myocardial damage.

How dysregulation of the immune system promotes diabetes mellitus and cardiovascular risk complications.

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia due to insulin resistance or failure to produce insulin. Patients with DM develop microvascular complications that include chronic kidney disease and retinopathy, and macrovascular complications that mainly consist in an accelerated and more severe atherosclerosis compared to the general population, increasing the risk of cardiovascular (CV) events, such as stroke or myocardial infarction by 2- to 4-fold. DM is commonly associated with a low-grade chronic inflammation that is a known causal factor in its development and its complications. Moreover, it is now well-established that inflammation and immune cells play a major role in both atherosclerosis genesis and progression, as well as in CV event occurrence. In this review, after a brief presentation of DM physiopathology and its macrovascular complications, we will describe the immune system dysregulation present in patients with type 1 or type 2 diabetes and discuss its role in DM cardiovascular complications development. More specifically, we will review the metabolic changes and aberrant activation that occur in the immune cells driving the chronic inflammation through cytokine and chemokine secretion, thus promoting atherosclerosis onset and progression in a DM context. Finally, we will discuss how genetics and recent systemic approaches bring new insights into the mechanisms behind these inflammatory dysregulations and pave the way toward precision medicine.

Triglyceride-Rich Lipoproteins: Their Role in Atherosclerosis.

The term "triglyceride-rich lipoproteins" (TRLs) includes chylomicrons and their remnants, very low-density lipoproteins (VLDL), and intermediate-density lipoproteins (IDL). In this manuscript, the mechanisms by which atherogenic TRLs contribute to the formation of atheroma plaques are reviewed. Cholesterol from TRLs that can be retained in the subendothelial space (i.e., remnants, DLs, and small VLDLs) contributes to the genesis of atherosclerosis. Triglycerides of atherogenic TRLs induce inflammation of the arterial wall. Mechanisms that explain the involvement of TRLs in atherosclerosis are the generation of pro-atherogenic changes in high-density lipoproteins and low-density lipoproteins, accumulation of TRLs in plasma, and their passage to the subendothelial space where they cause endothelial dysfunction and inflammation of the vascular wall. Furthermore, plasma accumulation of TRLs causes hyperviscosity and a procoagulant state. Finally, this manuscript summarizes the controversial aspects of the clinical approach and the treatment of cases with dyslipidemia explained by atherogenic TRLs.

LncRNA CASC7 regulates pathological progression of ox-LDL-stimulated atherosclerotic cell models via sponging miR-21 and regulating PI3K/Akt and TLR4/NF-κB signaling pathways.

Atherosclerosis (AS) is a frequently occurring cause of cardiovascular disease and involves a complicated pathophysiological process. Studies suggest that long non-coding RNAs (lncRNAs) are involved in AS genesis and progression, but mechanisms underlying these connections are unclear. Therefore, this work focused on exploring the role of lncRNA CASC7 in AS. In this study, RNA-seq sequencing results identified 1040 lncRNAs differentially expressed between AS patients and healthy controls. Of these lncRNAs, 458 were up-regulated and 582 were downregulated. CASC7 was found to be down-regulated in serum samples from AS patients and in HUVEC and VSMC exposed to ox-LDL. Overexpression of CASC7 inhibited proliferation and enhanced apoptosis of VSMC, and it markedly reduced IL-1β, IL-6 and TNF-α levels in HUVEC. Increased expression of a CASC7 target, miR-21, abolished the effects of CASC7 on HUVEC and VSMC. Notably, miR-21 targets PI3K in VSMC and TLR4 in HUVEC. The inhibitory effect of CASC7 was decreased by stimulation of PI3K, suggesting that the CASC7/miR-21 axis functions through PI3K/Akt signaling in VSMC. Similarly, the inhibitory effect of CASC7 on the inflammatory response in HUVEC was abolished through activating the TLR4/NF-κB signaling pathway. CASC7 inhibited proliferation and enhanced the apoptosis of VSMC through modulating the miR-21/PI3K-AKT axis, and upregulating CASC7 suppressed the inflammatory response of HUVEC by sponging miR-21 to inhibit the TLR4/NF-κB signal pathway.

Sequencing Analysis of mRNA Profile in Endothelial Cells in Response to ox-LDL.

The pathogenesis of atherosclerosis (AS) and abnormal endothelial cells apoptosis is a multifactorial biological process. Oxidized low density lipoprotein (ox-LDL) is a critical factor in the formation of AS. However, the exact mechanism is still not clear. Therefore, the aim of this study was to investigate some genes and biological pathways in endothelial cells apoptosis in response to ox-LDL. First, our results has validated that ox-LDL is an effective inducer of endothelial cells apoptosis, then, transcriptome sequencing was used to detect differential expression genes. In total, 71 differentially expressed genes (DEGs) were identified, including 32 upregulated genes and 39 downregulated genes. GO analysis showed that DEGs were mainly enriched in cytokine-mediated signaling pathway, gene expression, external side of plasma membrane, steroid binding, and signaling receptor binding. After KEGG analysis, the DEGs mainly focused on the following biochemical signaling pathways, including Signaling molecules and interaction (such as ICOSLG, IL6, ITGAM, TNFRSF13C and VTCN1), Signal transduction (such as IL13RA2, IL6, ITGAM, PDE5A, SGK3 and TNFRSF13C), Immune system (such as FCGR2A, ICOSLG, IL6, ITGAM and TNFRSF13C), and so on. These genes may play a dominant role in HAECs apoptosis and AS genesis. The above prediction and analysis provide an important basis for our follow-up study of the mechanism of these genes, which might be used as molecular targets or diagnostic biomarkers for AS.

Hyperhomocysteinemia: Focus on Endothelial Damage as a Cause of Erectile Dysfunction.

Erectile Dysfunction (ED) is defined as the inability to maintain and/or achieve a satisfactory erection. This condition can be influenced by the presence of atherosclerosis, a systemic pathology of the vessels that also affects the cavernous arteries and which can cause an alteration of blood flow at penile level. Among the cardiovascular risk factors affecting the genesis of atherosclerosis, hyperhomocysteinemia (HHcys) plays a central role, which is associated with oxidative stress and endothelial dysfunction. This review focuses on the biological processes that lead to homocysteine-induced endothelial damage and discusses the consequences of HHcys on male sexual function

TRANSFER OF HUMAN HAIR EXOCUTICLES ONTO GLASS BY LIQUID CATALASE AND WHOLE BLOOD (REPORTING BLOOD CLUMPING FORMATION WHEN CONTACT WITH KERATIN AS POSSIBLE FACTOR IN ATHEROSCLEROSIS)

The genesis of cardiovascular diseases, namely intra-arterial plaques formation leading to heart attacks, strokes and other vascular complication remains unanswered. To date there is accumulated evidence attributing antioxidant activity (toxic materials) of biochemical events in the human body as probable cause for the illness. Experts in the area of cardiovascular diseases have identified a lack of standardization in disease management; therefore, clinical trials comparing antioxidant agents (such as catalase) have been difficult to compare. Experts are also calling for new knowledge in relation to blood antioxidants physiology. Keratin is a chemical present in cellular structures in the body, also present in the human hair root and shaft. This manuscript presents a new finding, which is documentation of a binding capacity of catalase with keratin. Red blood cell are the main carriers of the catalase present in the circulatory system; in this manuscript experiments are introduced in support of a hypothesis adding one additional factor in the genesis of atherosclerosis; which is the protein enzyme catalase ever present in erythrocytes reacting with the keratin present in human arteries via an unknown mechanism.

From Endothelium to Lipids, Through microRNAs and PCSK9: A Fascinating Travel Across Atherosclerosis.

Lipids and endothelium are pivotal players on the scene of atherosclerosis and their interaction is crucial for the establishment of the pathological processes. The endothelium is not only the border of the arterial wall: it plays a key role in regulating circulating fatty acids and lipoproteins and vice versa it is regulated by these lipidic molecules thereby promoting atherosclerosis. Inflammation is another important element in the relationship between lipids and endothelium. Recently, proprotein convertase subtilisin/kexin type 9 (PCSK9) has been recognized as a fundamental regulator of LDL-C and anti-PCSK9 monoclonal antibodies have been approved for therapeutic use in hypercholesterolemia, with the promise to subvert the natural history of the disease. Moreover, growing experimental and clinical evidence is enlarging our understanding of the mechanisms through which this protein may facilitate the genesis of atherosclerosis, independently of its impact on lipid metabolism. In addition, environmental stimuli may affect the post-transcriptional regulation of genes through micro-RNAs, which in turn play a key role in orchestrating the crosstalk between endothelium and cholesterol. Advances in experimental research, with development of high throughput techniques, have led, over the last century, to a tremendous progress in the understanding and fine tuning of the molecular mechanisms leading to atherosclerosis. Identification of pivotal keystone molecules bridging lipid metabolism, endothelial dysfunction and atherogenesis will provide the mechanistic substrate to test valuable targets for prediction, prevention and treatment of atherosclerosis-related disease.

Postprandial dyslipidemia in insulin resistant states in adolescent populations.

Obesity and the metabolic syndrome are becoming increasingly prevalent not only in adults, but also in adolescents. The metabolic syndrome, a complex cluster of metabolic abnormalities, increases one's risk of developing type 2 diabetes and cardiovascular disease (CVD). Dyslipidemia, a key component of the metabolic syndrome, is highly associated with insulin resistance and contributes to increased CVD risk. Dyslipidemia has traditionally been assessed using a fasting lipid profile [i.e. fasting triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)]. However, the postprandial state predominates over the course of a day and non-fasting triglycerides independently predict CVD risk. In insulin resistant states, the intestine overproduces triglyceride-rich lipoprotein (TRL) particles, termed chylomicrons (CMs), following ingestion of a fat-containing meal, as well as in the fasting state. Along with elevated hepatic TRLs (i.e. very-low density lipoproteins), CMs contribute to remnant lipoprotein accumulation, small dense LDL particles, and reduced HDL-C, which collectively increase CVD risk. Given the early genesis of atherosclerosis and physiological metabolic changes during adolescence, studying postprandial dyslipidemia in the adolescent population is an important area of study. Postprandial dyslipidemia in the pediatric population poses a significant public health concern, warranting a better understanding of its pathogenesis and association with insulin resistance and CVD. This review discusses the metabolic syndrome, focusing on the link between insulin resistance, postprandial dyslipidemia, and CVD risk. Furthermore, the clinical significance and functional assessment of postprandial dyslipidemia, specifically in the adolescent population, is discussed in more detail.

Repeated Porphyromonas gingivalis W83 exposure leads to release pro-inflammatory cytokynes and angiotensin II in coronary artery endothelial cells

The role of Porphyromonas gingivalis (P. gingivalis) or its virulence factors, including lipopolysaccharide (LPS) not only has been related with periodontitis but also with endothelial dysfunction, a key mechanism involved in the genesis of atherosclerosis and hypertension that involving systemic inflammatory markers as angiotensin II (Ang II) and cytokines. This study compares the effect of repeated and unique exposures of P. gingivalis W83 LPS and live bacteria on the production and expression of inflammatory mediators and vasoconstrictor molecules with Ang II. Human coronary artery endothelial cells (HCAEC) were stimulated with purified LPS of P. gingivalis (1.0, 3.5 or 7.0 μg/mL) or serial dilutions of live bacteria (MOI 1: 100 - 1:0,1) at a single or repeated exposure for a time of 24 h. mRNA expression levels of AGTR1, AGTR2, IL-8, IL-1β and MCP-1 were determined by RT-qPCR, and IL-6, MCP-1, IL-8, IL-1β and GM-CSF levels were measured by flow cytometry, ELISA determined Ang II levels. Live bacteria in a single dose increased mRNA levels of AGTR1, and repeated doses increased mRNA levels of IL-8 and IL-1β (p < 0.05). Repeated exposure of live-P. gingivalis induced significant production IL-6, MCP-1 and GM-CSF (p < 0.05). Moreover, these MCP-1, IL-6 and GM-CSF levels were greater than in cells treated with single exposure (p < 0.05), The expression of AGTR1 and production of Ang II induced by live-P. gingivalis W83 showed a vasomotor effect of whole bacteria in HCAEC more than LPS. In conclusion, the findings of this study suggest that repeated exposure of P. gingivalis in HCAEC induces the activation of proinflammatory and vasoconstrictor molecules that lead to endothelial dysfunction being a key mechanism of the onset and progression of arterial hypertension and atherosclerosis.

CT Attenuation of Pericoronary Adipose Tissue in Normal Versus Atherosclerotic Coronary Segments as Defined by Intravascular Ultrasound.

The factors influencing genesis of atherosclerosis at specific regions within the coronary arterial system are currently uncertain. Local mechanical factors such as shear stress as well as metabolic factors, including inflammatory mediators released from epicardial fat, have been proposed. We analyzed computed tomographic (CT) attenuation of pericoronary adipose tissue in normal versus atherosclerotic coronary segments as defined by intravascular ultrasound (IVUS). We evaluated the data sets of 29 patients who were referred for invasive coronary angiography and in whom IVUS of 1 coronary vessel was performed for clinical reasons. Coronary CT angiography was performed within 24 hours from invasive coronary angiography. Computed tomographic angiography was performed using dual-source CT (Siemens Healthcare; Forchheim, Germany). A contrast-enhanced volume data set was acquired (120 kV, 400 mA/rot, collimation 2 × 64 × 0.6 mm, 60-80 mL intravenous contrast agent). Intravascular ultrasound was performed using a 40-MHz IVUS catheter (Atlantis; Boston Scientific Corporation, Natick, Mass) and motorized pullback at 0.5 mm/s. Sixty corresponding coronary artery segments within the coronary artery system were identified in both dual source computed tomography and IVUS using bifurcation points as fiducial markers. In dual source computed tomography data sets, 8 serial parallel cross sections (2-mm slice thickness) were rendered orthogonal to the center line of the coronary artery for each segment. For each cross section, pericoronary adipose tissue within a radius of 3 mm from the coronary artery and enclosed within the epicardium (excluding coronary veins and myocardium) was manually traced and mean CT attenuation values were obtained. Intravascular ultrasound was used to define coronary segments as follows: presence of predominantly fibrous atherosclerotic plaque (hyperechoic), presence of predominantly lipid-rich atherosclerotic plaque (hypoechoic), and absence of atherosclerotic plaque. In IVUS, 20 coronary segments with fibrous plaque, 20 segments with lipid-rich plaque, and 20 coronary segments without plaque were identified. The mean CT attenuation of pericoronary adipose tissue for segments with any coronary atherosclerotic plaque was -34 ± 14 Hounsfield units (HU), as compared with -56 ± 16 HU for segments without plaque (P = 0.005). The density of pericoronary fat in segments with fibrous versus lipid-rich plaque as defined by IVUS was not significantly different (-35 ± 19 HU vs -36 ± 16 HU, P = 0.8). Mean CT attenuation of pericoronary adipose tissue is significantly lower for normal versus atherosclerotic coronary segments. This supports a hypothesis of different types of pericoronary adipose tissue, the more metabolically active of which might exert local effects on the coronary vessels, thus contributing to atherogenesis.

Evaluation of the artherogenic potential of homocysteine and its cytotoxic effect on HUVECs

Background: In recent decades, several studies have shown that hyperhomocysteinemia is an independent risk factor for atherosclerosis. The objective of this work is, first, to assess the atherogenic potential of homocysteine in rats and and appraise its effect on endothelial cells: the main components of the blood vessel.&#x0D; Methods: In the in vivo study, hyperhomocysteinemia is induced in rats by a diet supplemented with L-methionine (1 g/kg/day). After 21 days of treatment, a blood sample is performed for biochemical study (total cholesterol, triglycerides, HDL, LDL cholesterol, ALT, AST, CRP, and total protein) and a removal of organs (aorta, liver, and heart) for the assay MDA and histological study. For the in vitro study, HUVECs were cultured for 24 h then exposed to various concentrations of homocysteine (2 mM, 4 mM, 8 mM). After 24 hours, we confirm the cellular phenotype and its number.&#x0D; Results: The angiotoxic dose of methionine induces a significant increase for all biochemical parameters (except HDL-C, which is diminished). In addition, an alteration of the histological structure of the aorta (appearance of foam cells) of the liver (steatosis) and of the heart. The in vitro study revealed a senescent phenotype of HUVECs and an inhibition of cell proliferation.&#x0D; Conclusion: Our results suggest that homocysteine is involved in the genesis of atherosclerosis by affecting directly the endothelial cells.

Apolipoprotein B-containing lipoproteins and atherosclerotic cardiovascular disease.

Cholesterol-rich, apolipoprotein B (apoB)-containing lipoproteins are now widely accepted as the most important causal agents of atherosclerotic cardiovascular disease. Multiple unequivocal and orthogonal lines of evidence all converge on low-density lipoprotein and related particles as being the principal actors in the genesis of atherosclerosis. Here, we review the fundamental role of atherogenic apoB-containing lipoproteins in cardiovascular disease and several other humoral and parietal factors that are required to initiate and maintain arterial degeneration. The biology of foam cells and their interactions with high-density lipoproteins, including cholesterol efflux, are also briefly reviewed.

Role of Oxidative Stress in the Genesis of Atherosclerosis and Diabetes Mellitus: A Personal Look Back on 50 Years of Research.

We have provided an overview, based on the literature and our data. In accordance with the theory of D. Harman free radical processes cause damages that can accumulate and contribute to aging of the organism. Atherosclerosis and diabetes are developing for a long time so they are manifested predominantly in old age. We found an increase in the level of free radical peroxidation products and decrease in the activity of antioxidant enzymes in the tissues of animals with experimental atherosclerosis. Similar changes were found in the blood of patients with atherosclerosis and aortic autopsy material with atherosclerotic lesions. Thus, it was revealed that oxidative stress occured under atherosclerosis, and the arteriosclerosis to &quot;Free Radical Pathologies&quot; was attributed. Later it was discovered by different authors that oxidized Low Density Lipoproteins (LDL) and malonyldialdehyde- modified LDL accumulated during atherogenesis, causing damages of vascular wall. Under diabetic hyperglycemia glucose co-oxidized during free radical lipoperoxidation. This process promoted the transformation of oxidative stress to carbonyl stress with accumulation of biologically active dicarbonyls, including glyoxal and methylglyoxal. We show that the glyoxal-modified LDL were captured by cultured macrophages with a higher efficiency than the MDA-modified LDL. This could facilitate the more rapid development of lipoidosis in the vessel wall (due to the formation of foam cells) and manifestation of atherosclerosis under diabetes. We found that in patients with diabetes there was a sharp decrease in the activity of antioxidant enzymes as a result of the modification of the active center under development of carbonyl stress. We expressed a hypothesis about a common molecular mechanism of vascular wall damages under atherosclerosis and diabetes.

Etiopathogenesis of Central Nervous System Gliomas

There is much evidence that gliomas are caused by progressive ischemia, followed by increasing and prolonged hypoxia very close to the subventricular zone. In this way, hypoxia on immature glial cells is the primary cause in gliomas genesis. The ischemic process caused by atherosclerosis, anatomical variants of the arteries in the affected area and associated with carcinogenic agents are the harmful factors. While cytotoxic hypoxia triggers a reactive oxygen species (ROS) overproduction in the glial progenitor cells. Consequently, cellular impairment caused by ROS alters the cell cycle phases and provokes genesis of low-grade glioma. Subsequently, its progression causes angiogenesis and higher-grade cancer cells. Then, the vascular recanalization through aspirin is the indicated therapy to reduce the ischemic process by increasing blood flow and oxygen in the affected zone. Therefore, we must fight against the genesis of atherosclerosis and thus decrease the incidence of “neurodegenerative” diseases and cancer.

Statine et pathologies cardiovasculaires après 75 ans

Statin prescription in persons older than 75 years or with frailty signs raises questions on the role of cholesterol in the genesis of atherosclerosis in this population, on the benefit of this treatment in primary or secondary prevention, and on their side effects in a context of multiple pathology and multiple medications. These questions are approached with the available literature data for this population. In secondary prevention, statin prescription is recommended whatever the age although intensive treatment should be avoided. In primary prevention, in the absence of consensus, their prescription depends on both geriatric and cardiovascular risk assessment.