Atheroma Formation Research Articles

Mitochondrial DAMPs and altered mitochondrial dynamics in OxLDL burden in atherosclerosis

Atherosclerosis results in life-threatening cardiovascular pathologies, including ischemic heart disease, stroke, myocardial infarction, and peripheral arterial disease. The role of increased serum low-density lipoprotein (LDL) and resultant accumulation of oxidized-LDL (oxLDL) in atheroma formation is well established. Recent findings elucidate the significance of mitochondrial damage-associated molecular patterns (mtDAMPs) in triggering sterile inflammation in concert with oxLDL. The mtDAMPs including mitochondrial DNA (mtDNA), cytochrome C, cardiolipin, heat shock protein 60 (HSP60), mitochondrial transcription factor A (TFAM), and N-formyl peptides, are expected to possess proatherogenic roles. However, limited data are available in the literature. The mtDAMPs initiate sterile inflammation in atherosclerotic lesions via numerous signaling pathways, most of which converge to the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome. Priming the activation of the NLRP3 inflammasome, mtDAMPs promote secretion of proinflammatory cytokines, including interleukin-1β (IL-1β), implicated in atherosclerotic lesions through vascular smooth muscle and fibroblast proliferation, arterial wall thickening, and plaque formation. In this article we critically reviewed and discussed the central role of the NLRP3 inflammasome in mtDAMP-induced sterile inflammation in atherosclerosis with specific components including caspase-1, pregnane X receptor (PXR), adenosine monophosphate activated protein kinase (AMPK), protein phosphatase 2A (PP2A), thioredoxin-interacting protein (TXNIP), and downstream cytokines including IL-1β and IL-18 as potential mediators of atherosclerosis. Better understanding of the proinflammatory effects of mtDAMPs and its pathological association with oxLDL possess immense translational significance for novel therapeutic intervention.

Association Between Periodontal Disease and Atherosclerotic Cardiovascular Diseases: Revisited.

Atherosclerotic cardiovascular disease (ACVD) is an inflammatory disease of the coronary arteries associated with atheroma formation, which can cause disability and often death. Periodontitis is ranked as the sixth most prevalent disease affecting humans affecting 740 million people worldwide. In the last few decades, researchers have focused on the effect of periodontal disease (PD) on cardiovascular disease. The aim of this review was to investigate the association between these two diseases. PD is a potential risk factor that may initiate the development, maturation, and instability of atheroma in the arteries. Two mechanisms were proposed to explain such association, either periodontal pathogens directly invade bloodstream or indirectly by increasing systemic level of inflammatory mediators. Interestingly, it has been suggested that improvement in the condition of one disease positively impact the condition of the other one. Highlighting the association between these two diseases, the importance of early diagnosis and treatment of PD and its impact on cardiovascular status may be of great value in reducing the complications associated with ACVDs. Further in vitro and in vivo studies with longer follow up are necessary to confirm the causal relationship between PD and ACVDs.

LONGEST LAD ENDARTRECTOMY RECORDED AND DOCUMENTED TILL DATE IN AFIC/NIHD

As the world advances, living standards are getting changed with inclination more toward sedentary life style and junk food, we are seeing a worldwide increased incidence of coronary artery disease. A 73 year of age gentleman with progressive shortness of breath NYHA-II/III since last 6 months and epigastric discomfort with effort angina CCS-III. Was having no other co-morbidities, except of 35 pack years of smoking. On evaluation his Coro-angiogram revealed Diffuses TVCAD with Lad diffusely diseased throughout its middle course >90%, LCX 80%, RCA mid-Course critical discrete lesion of 90%. His 2D, TTE showed normal valvular apparatus and ejection fraction of 55%. Literature review further furnishes the fact that LAD is most commonly being affected by atheroma formation hence making it the most common site for endartrectomy, though peri-operative MI is still a grave concern, but half dose protamine slow reversal of the heparin and keeping ACT at 150-160 sec greatly reduces the incidence of peri-operative MI.

Genetics of Adult Onset Stroke Subtypes: A Review of Current Knowldege and Future Prospects

The genetic contribution in stroke onset depends on the stroke subtypes. Understanding the genetic mechanism may influence the future direction in stroke management. There is complex interplay of genetic and environmental factors for any stroke event. Very small proportion of stroke is attributable to mendelian disorders. Stroke may also manifest as part of a syndromic disease in the form of single gene multisystem disorder. But there is no direct contribution of genetic polymorphism in conventional stroke subtypes. Specific genetic loci increase the suspectibility to development of hypertension, diabetes, dyslipideamia or influence the coagulation pathway or chance of atheroma formation and embolism. While chr9p21 locus or PITX2 and ZFHX3 are related to cardioemetabolic, HDAC9, TSPAN2 and 9p21 locus are responsible for the large vessel occlusion. On the otherhand, genome-wide significant locus on chromosome 1q22 the APOE locus are found to have significant association with intracerebral hemorrhage. But the direct pathophysiologic relationship of genetic plymorphirsm may be linked to onset of sub arachnoid hemorrhage. MMP-3, endothelial nitric oxide synthase (eNOS), tumor necrosis factor (TNF)-α, VCAM-1 etc have been found to be responsible for intracranial aneurysm formation, growth and risk of rupture.
 Journal of National Institute of Neurosciences Bangladesh, January 2021, Vol. 7, No. 1, pp. 75-86

Ateroma arteri karotis pada radiograf panoramik sebagai diagnosis awal aterosklerosis

Objectives: This review aimed to understand the radiographic features of carotid artery atheroma on panoramic radiographs as an early diagnosis of atherosclerosis. 
 Literature Review: Carotid artery calcification is caused by a plaque known as an atheroma. Atheroma is a plaque composed of lipids and rich in calcium. If atheroma formation in the carotid arteries increases, it would cause stenosis of the blood vessels and increase the risk of stroke. On panoramic radiographs, carotid artery atheroma appears as a heterogeneous radiopaque image with an irregular shape and well-defined borders. Radiopaque image located inferior to the angle of the mandible, close to the cervical spine (C3-C5) and above the hyoid bone.
 Conclusion: Incidental findings on panoramic radiograph could be an initial reference for further examination and evaluation of atherosclerosis.

Targeting porphyromonas gingivalis to treat Alzheimer’s disease and comorbid cardiovascular disease

AbstractBackgroundWe recently demonstrated the presence of the bacterial pathogen, Porphyromonas gingivalis (Pg), and its protease virulence factors, known as gingipains, in greater than 90% of AD brains. Brain gingipain levels significantly correlated with AD diagnosis and tau and ubiquitin pathology. Mechanistic studies in wild type mice demonstrated that Pg invades the brain after infection of the oral cavity, resulting in the development of neuropathology consistent with that of AD. These effects were blocked in mice after oral administration of the gingipain inhibitor COR388. In addition to neuropathology, AD is often accompanied by the comorbidity of cardiovascular disease. Pg has been linked to the development of atherosclerosis and the bacteria are found abundant within atheromatous plaque. We investigated if COR388 was efficacious in treating Pg‐accelerated atherosclerosis in a rabbit model.MethodEighteen New Zealand White rabbits on a 13‐week regimen of 0.5% cholesterol diet to induce atherosclerosis were randomized in the study. Twelve rabbits were orally infected with Pg 3x/week for 6 weeks for oral disease induction and 6 rabbits were sham‐infected. Six Pg –infected rabbits were orally administered COR388 10mg/kg once daily for the entire 13 weeks of the study (prevention protocol), and 6 Pg‐infected rabbits received vehicle for 13 weeks. Six sham‐infected rabbits received vehicle for 13 weeks. At 13 weeks, atherosclerotic plaques were quantified by assessing Sudan IV staining, histology, and ex vivo MRI. Serum levels of C‐reactive protein (CRP) were evaluated as a measure of systemic inflammation.ResultPg‐infected rabbits exhibited accelerated atherosclerotic disease severity than sham‐infected animals. COR388 diminished this atherogenesis compared to vehicle controls as evidenced by significantly less arterial plaque and a lower intima/media ratio. COR388 treatment also significantly reduced systemic levels of CRP.ConclusionCOR388, a novel lysine‐gingipain inhibitor, is currently being tested in a Phase 2/3 clinical trial to target Pg for the treatment of AD. Based on the current preclinical data reported here, COR388 has the potential to attenuate atheroma formation and systemic inflammation in Pg‐ induced atherosclerosis and therefore may have beneficial effects on comorbid cardiovascular disease in Pg‐associated AD.

Enterohepatic Transcription Factor CREB3L3 Protects Atherosclerosis via SREBP Competitive Inhibition.

Background & AimscAMP responsive element-binding protein 3 like 3 (CREB3L3) is a membrane-bound transcription factor involved in the maintenance of lipid metabolism in the liver and small intestine. CREB3L3 controls hepatic triglyceride and glucose metabolism by activating plasma fibroblast growth factor 21 (FGF21) and lipoprotein lipase. In this study, we intended to clarify its effect on atherosclerosis.MethodsCREB3L3-deficifient, liver-specific CREB3L3 knockout, intestine-specific CREB3L3 knockout, both liver- and intestine-specific CREB3L3 knockout, and liver CREB3L3 transgenic mice were crossed with LDLR−/− mice. These mice were fed with a Western diet to develop atherosclerosis.ResultsCREB3L3 ablation in LDLR−/− mice exacerbated hyperlipidemia with accumulation of remnant APOB-containing lipoprotein. This led to the development of enhanced aortic atheroma formation, the extent of which was additive between liver- and intestine-specific deletion. Conversely, hepatic nuclear CREB3L3 overexpression markedly suppressed atherosclerosis with amelioration of hyperlipidemia. CREB3L3 directly up-regulates anti-atherogenic FGF21 and APOA4. In contrast, it antagonizes hepatic sterol regulatory element-binding protein (SREBP)–mediated lipogenic and cholesterogenic genes and regulates intestinal liver X receptor–regulated genes involved in the transport of cholesterol. CREB3L3 deficiency results in the accumulation of nuclear SREBP proteins. Because both transcriptional factors share the cleavage system for nuclear transactivation, full-length CREB3L3 and SREBPs in the endoplasmic reticulum (ER) functionally inhibit each other. CREB3L3 promotes the formation of the SREBP-insulin induced gene 1 complex to suppress SREBPs for ER-Golgi transport, resulting in ER retention and inhibition of proteolytic activation at the Golgi and vice versa.ConclusionsCREB3L3 has multi-potent protective effects against atherosclerosis owing to new mechanistic interaction between CREB3L3 and SREBPs under atherogenic conditions.

DPP-4 Inhibitor Linagliptin Ameliorates Oxidized LDL-Induced THP-1 Macrophage Foam Cell Formation and Inflammation.

IntroductionAtherosclerosis is one of the major causes of cardiovascular diseases. Lipid uptake and accumulation in macrophages play a major role in atherosclerotic plaque formation from its initiation to advanced atheroma formation. The dipeptidyl peptidase-4 (DPP-4) inhibitor Linagliptin is commonly used to lower blood glucose in type 2 diabetes patients. Recent studies report that Linagliptin has cardiovascular protective and anti-inflammatory effects.MethodsTHP-1 macrophage cells were treated with 100 nM PMA for 72 hour to induce foam cell formation. The differentiated cells were exposed to 100 μg/mL ox-LDL in the presence or absence of the DPP-4 inhibitor Linagliptin. The expression levels of DPP-4 and inflammatory cytokines were detected by RT-PCR, ELISA, and Western blot experiments. The cellular ROS level was measured by staining the cells with the fluorescent probe DCFH-DA. The separation of lipoprotein fractions was achieved by high-performance liquid chromatography (HPLC). The cells were labeled with fluorescent-labeled cholesterol to measure cholesterol efflux, and lipid droplets were revealed by Nile red staining.ResultsThe presence of Linagliptin significantly reduced ox-LDL-induced cytokine production (IL-1β and IL-6) and ROS production. Linagliptin ameliorated ox-LDL-induced lipid accumulation and impaired cholesterol efflux in macrophages. Mechanistically, this study showed that Linagliptin mitigated ox-LDL-induced expression of the scavenger receptors CD36 and LOX-1, but not SRA. Furthermore, Linagliptin increased the expression of the cholesterol transporter ABCG1, but not ABCA1.ConclusionLinagliptin possesses a potent inhibitory effect on THP-1 macrophage-derived foam cell formation in response to ox-LDL. This effect could be mediated through a decrease in the expression of CD36 and LOX-1 on macrophages and an increase in the expression of the cholesterol transporter ABCG1. This study indicates that the DPP-4 inhibitor Linagliptin plays a critical role in preventing foam cell formation in vitro. However, future research using an atherosclerotic animal model is necessary to determine its effectiveness and to prove its potential implication in the prevention and treatment of atherosclerosis.

Miniaturized Piezo Force Sensor for a Medical Catheter and Implantable Device.

Real-time monitoring of intrabody pressures can benefit from the use of miniaturized force sensors during surgical interventions or for the recovery period thereafter. Herein, we present a force sensor made of poly(vinylidene fluoride)-co-trifluoroethylene (P(VDF-TrFE)) with a simple fabrication process that has been integrated into the tip of a medical catheter for intraluminal pressure monitoring, as well as into an implantable device with a power consumption of 180 μW obtained by the near-field communication (NFC) interface to monitor the arterial pulse at the subcutaneous level (≤1 cm). The pressure range supported by the sensor is below 40 kPa, with a signal responsivity of 0.63 μV/Pa and a mean lifetime expectancy of 400 000 loading cycles inside physiological conditions (12 kPa). The proposed sensor has been tested experimentally with synthetic anatomical models for the lungs (bronchoscopy) and subcutaneous tissue, as well as directly above the human carotid and radial arteries. Information about these pressure levels can provide insights about tissue homeostasis inside the body as fluid dynamics are altered in some health conditions affecting the hemodynamic and endocrine body systems, whereas for surgical interventions, precise control and estimation of the pressure exerted by a catheter over the internal walls are necessary to avoid endothelium injuries that lead to bleeding, liquid extravasation, or flow alteration associated with atheroma formation.

Assessment of Cardiovascular Safety of Anti-Osteoporosis Drugs.

The incidence of osteoporosis and cardiovascular disease increases with age, and there are potentially shared mechanistic associations between the two conditions. It is therefore highly relevant to understand the cardiovascular implications of osteoporosis medications. These are presented in this narrative review. Calcium supplementation could theoretically cause atheroma formation via calcium deposition, and in one study was found to be associated with myocardial infarction, but this has not been replicated. Vitamin D supplementation has been extensively investigated for cardiac benefit, but no consistent effect has been found. Despite findings in the early 21st century that menopausal hormone therapy was associated with coronary artery disease and venous thromboembolism (VTE), this therapy is now thought to be potentially safe (from a cardiac perspective) if started within the first 10 years of the menopause. Selective estrogen receptor modulators (SERMs) are associated with increased risk of VTE and may be related to fatal strokes (a subset of total strokes). Bisphosphonates could theoretically provide protection against atheroma. However, data from randomised trials and observational studies have neither robustly supported this nor consistently demonstrated the potential association with atrial fibrillation. Denosumab does not appear to be associated with cardiovascular disease and, although parathyroid hormone analogues are associated with palpitations and dizziness, no association with a defined cardiovascular pathology has been demonstrated. Finally, romosozumab has been shown to have a possible cardiovascular signal, and therefore post-market surveillance of this therapy will be vital.

Repeatedly heated mix vegetable oils-induced atherosclerosis and effects of Murraya koenigii

BackgroundStatins are considered as standard drugs to control cholesterol levels, but their use is also associated with renal hypertrophy, hemorrhagic stroke, hepatomegaly, and myopathy. Murraya koenigii is an herb that is used in traditional cuisine and as a medicine in South Asia. Here we assessed the antidyslipidemic and antiatherosclerotic effects of this spice in repeated heated mix vegetable oils (RHMVO)-induced atherosclerotic models.MethodsAqueous extract of M. koenigii leaves (Mk LE) was prepared and its phytoconstituents were determined. Rabbits were divided into 5 groups (n = 10). Except for the control group, all the other four groups were treated with RHMVO for 16 weeks (dose = 2 ml/kg/day) to induce dyslipidemia and atherosclerosis. These groups were further treated for 10 weeks either with 300 and 500 mg/kg/day Mk LE, lovastatin, RHMVO, or left untreated. Body and organ weights were measured along with oxidative stress and tissue damage parameters. Lipid profile and hepatic function markers were studied. Atheroma measurement and histopathological examination were also performed in control and treated groups.ResultsMk LE significantly (p < 0.05) attenuated RHMVO-induced dyslipidemia and atheroma formation. Furthermore, fat accumulation and lipid peroxidation in hepatic tissues were reduced by Mk LE in a dose-dependent manner. Our results indicated that the antidyslipidemic effects of Mk LE in 500 mg/kg/day dose were comparable to lovastatin. Additionally, oxidative stress markers were reduced much more significantly in Mk LE-500 than in the statin group (p < 0.05).ConclusionsThis study recommends Mk LE as a potent antioxidant and lipid-lowering natural medicine that can attenuate the RHMVO-induced atherosclerotic in optimal doses and duration. Therefore, Mk LE can be accessible, cheap, and free of adverse effects alternate to statins.

HPV infection as a risk factor for atherosclerosis: A connecting hypothesis

Atheromatous plaques occurring in large arteries are common and life-threatening lesions. Multiple factors are involved in the pathogenesis of atheromatous plaques, such as hyperlipidaemia and hypercholesterolaemia, high blood pressure and chronic systemic inflammation. Recent findings have suggested that infection with high-risk human papillomavirus (HPV) may increase the risk of developing atheromatous plaques. However, HPV is considered a tissue-specific virus with a strong tropism towards squamous epithelial cells, and the mechanisms whereby it may promote the development of atheromas remain unclear. Here, we propose a connecting hypothesis to explain the possible causative role of HPV on atheroma development. We hypothesize that HPV infection may promote atheroma formation in infected patients by enhancing systemic inflammation or by directly targeting blood vessels via nucleic acids carried by extracellular vesicles such as exosomes. The pro-inflammatory effects of HPV and the release of extracellular vesicles by HPV-transformed cells are well documented in scientific literature. Possible experimental approaches to test this hypothesis are also discussed, especially experiments employing transgenic mice bearing HPV16 transgenes. If correct, this hypothesis would have major implications for the prevention of cardiovascular diseases, especially due to the preventable nature of HPV infection through vaccination.

Clopidogrel Prophylaxis Abates Myocardial Ischemic Injury and Inhibits the Hyperlipidemia-Inflammation Loop in Hypercholestrolemic Mice

Platelet hyper adhesiveness orchestrates with inflammation and vascular muscle proliferation leading to atheroma formation and endothelial dysfunction. The current study aims to compare the prophylactic role of Aspirin and Clopidogrel therapy against isoproterenol-induced acute myocardial infarction (AMI), in mice on high-fat, cholesterol-rich diet (HFD-C). The animals received HFD-C with Aspirin or Clopidogrel for 8weeks and were subjected to AMI by isoproterenol. The blood lipids, inflammatory cytokines, myocardial enzymes, redox state, long pentraxin (PTX3), and matrix metalloproteinases (MMP-2 and MMP-9) activities were investigated. Antiplatelet therapy moderated the hyperlipidemia induced by HFD-C in the current study. Essentially, the total cholesterol and LDL-C levels were lower with Aspirin than with Clopidogrel therapy. Yet Aspirin and Clopidogrel each comparably lowered CK-MB, AST, MMP-2, MMP-9, and the lipid peroxidation product malondialdehyde (MDA) in the hyperlipidemic animals exposed to AMI. However, the decline in cTn-T, LDH and PTX3 levels was greater after Clopidogrel than Aspirin administration. Therefore, Clopidogrel provides greater protection against AMI than Aspirin in the hyperlipidemic mice. This could be explained by the suppression of the proinflammatory cytokines IL-6, TNF-α, TGF-1β and stabilization of the extracellular matrix through the inhibition of MMP-2 and MMP-9 activities. Furthermore, Clopidogrel demonstrated significant antioxidative action in the AMI animals, resulting in diminished MDA production and preserved CAT activity. Beside its therapeutic role in the thrombotic vascular events, Clopidogrel confers significant protection against ischemic myocardial injury by counteracting the platelet-mediated inflammation and oxidative stress associated with HFD-C consumption in animals.

Effect of bariatric surgery in the evolution of oxidative stress depending on the presence of atheroma in patients with morbid obesity.

Morbid obesity is associated with accelerated atherosclerosis, a chronic vascular disease related to oxidative stress (OS) and endothelial dysfunction. We aimed to evaluate the effect of bariatric surgery (BS) on oxidative stress as a cardiovascular risk factor in patients with and without atheromatous plaques. Arnau de Vilanova University Hospital and University of Barcelona. Plasma samples from 66 patients with morbid obesity were obtained before BS and 6 and 12 months after. Patients were divided into 2 groups based on the presence of atheromatous plaques (detected by ultrasonography). OS parameters were measured by enzyme-linked immunosorbent assay. Patients with morbid obesity had OS independently of the presence of an atheroma, but oxidized low-density lipoprotein levels were higher in patients with plaques throughout the study (P = .0430). After surgery, oxidized low-density lipoprotein and malondialdehyde levels decreased significantly (P < .0001 in both cases). At the beginning of the study, antioxidant enzyme levels were the same between the groups. After surgery, paraoxonase 1 levels were increased (P < .0001) in the group without plaque, being significantly higher (P = .0147). Superoxide dismutase 2 levels were only decreased in patients without plaque (P < .0010), while catalase activity was higher in patients with plaque. Morbid obesity may lead to chronic OS, which increases predisposition to atherogenesis. BS improves the antioxidant profile and reduces OS and co-morbidities in both groups. However, the benefits are greater for patients without plaque. Therefore, BS may prevent atheroma formation and also could prevent plaque rupture by decreasing OS.

Mechanisms underlying the association between periodontitis and atherosclerotic disease.

Atherosclerosis is central to the pathology of cardiovascular diseases, a group of diseases in which arteries become occluded with atheromas that may rupture, leading to different cardiovascular events, such as myocardial infarction or ischemic stroke. There is a large body of epidemiologic and animal model evidence associating periodontitis with atherosclerotic disease, and many potential mechanisms linking these diseases have been elucidated. This chapter will update knowledge on these mechanisms, which generally fall into 2 categories: microbial invasion and infection of atheromas; and inflammatory and immunologic. With respect to the invasion and infection of atheromas, it is well established that organisms from the subgingival biofilm can enter the circulation and lodge in most distant tissues. Bacteremias resulting from oral interventions, and even oral hygiene activities, are well documented. More recently, indirect routes of entry of oral organisms (via phagocytes or dendritic cells) have been described for many oral organisms, into many tissues. Such organisms include the periodontal pathogens Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Tannerella forsythia, and Fusobacterium nucleatum. Intracellular survival of these organisms with dissemination to distant sites (The Trojan Horse approach) has been described. Their relative contribution to atheroma formation and progression has been studied mainly in experimental research, with results demonstrating that these organisms can invade endothelial cells and phagocytic cells within the atheroma, leading to pathogenic changes and progression of the atheroma lesion. The second category of mechanisms potentially linking periodontitis to atherosclerosis includes the dumping of inflammatory mediators originating from periodontal lesions into the systemic circulation. These inflammatory mediators, such as C-reactive protein, matrix metalloproteinases, fibrinogen, and other hemostatic factors, would further accelerate atheroma formation and progression, mainly through oxidative stress and inflammatory dysfunction. Moreover, direct effects on lipid oxidation have also been described. In summary, the evidence supports the concept that periodontitis enhances the levels of systemic mediators of inflammation that are risk factors for atherosclerotic diseases.

Dysfunctional HDL takes its Toll on the endothelial glycocalyx

Patients with end-stage renal disease have a high risk of dying from cardiovascular disease that cannot be explained solely by traditional cardiovascular disease risk factors. Hesse etal. suggest that dysfunctional high-density lipoprotein cholesterol generated in patients with end-stage renal disease causes endothelial glycocalyx degradation. Glycocalyx degradation may represent one of the earliest insults leading to atheroma formation, and so this work suggests a novel link between renal failure and cardiovascular disease.

ULTRASTRUCTURAL FEATURES OF HERPESVIRUS-INDUCED AORTIC INTIMA DAMAGE IN MICE FED THE HIGH-FAT DIET

The aim: To study the effect of a high-fat diet (HFD) on the structural changes in the aortic intima in intact and HSV-1-infected mice using Scanning electron microscopy (SEM) and Transmission electron microscopy (TEM). Materials and methods: In experiments Balb/c mice were infected with the HVS-1 and fed high-fat diet and 12 weeks later aortic ultrastructure was examined by SEM and TEM methods. The animals were subdivided into four experimental groups: 1st group - HSV-1-infected animals; 2nd - animals consuming high-fat diet (HFD); 3rd - infected animals that were subsequently consuming a high-fat diet (HSV / HFD); 4th - animals consuming a high-fat diet that were subsequently infected with HSV-1 (HFD / HSV) (n = 6); and control group - intact animals. Results: HVS-1 impaired ultrastructural changes in aorta greater than high-fat diet and HVS-1 alone (higher density of lipid inclusions in the subendothelial space, necrosis of endothelial cells), and infection of mice after high-fat diet ended 100% mortality. The formation of atheroma in the aortic wall during HFD was not detected, but the initiative manifestations of atherogenesis have been identified and restricted in the aortic intima. These structural changes included lipid inclusions in the subendothelial space, cell damage and destruction, which lead to an increase cellular detritus in the 3rd (HSV / HFD) group. Conclusions: HSV infection potentiates the accumulation of lipid inclusions in the aortic intima during a HFD, facilitates infection and contributes to the development of acute infection.

P4534The Mediterranean diet benefit in chronic heart failure by decoding central and peripheral vessel rheology, atheroma formation and serum prolactin levels

Abstract Background Central hemodynamics and especially wave reflection amplification exhibit a vital parameter of chronic heart failure (CHF) physiology. Erectile dysfunction (ED) displays a poor peripheral vessel rheology and serum prolactin role is still debated in CHF mechanisms. The Mediterranean diet (Med-diet) is famous for its vasoprotective and wellbeing properties. Purpose To investigate the effect of the Med-diet in central hemodynamics, erectile status, atheroma formation and serum prolactin levels in male patients with chronic heart failure. Methods 123 CHF male patients under optimal medical therapy enrolled the study (mean age: 65±8 yo, NYHA class II, ejection fraction &lt;40%). All underwent evaluation of the carotid – femoral pulse wave velocity (PWV), estimation of central pressures and augmentation index (AIx) as parameter of wave reflection amplification (sphygmocor device). Ejection fraction (EF) of the left ventricle was estimated by using 2D echocardiography (Simpson method). ED severity and adherence to the Med-diet were assessed by the SHIM-5 (range: 0–25) and the Med-diet (range: 0–55) scores. Higher values point to better erectile function and a great Med-diet compliance respectively. Detection of atheroma was based on the intima- media thickness (IMT) of the common carotid artery. Prolactin levels were assessed in morning blood samples taken before 09:00 am. Results The SHIM −5 score (mean: 12±4) was associated to the AIx (p=0,03, r=0,75) and both positively and strongly related to the Med-diet score (p=0,01, r=0,8 and p=0,01, r=0,75 respectively). Med-diet compliance was negatively associated to IMT (p=0,02, r=−0,8) and serum prolactin levels (p=0,03, r=−0,6).Moreover, we notice a positive association between prolactin and the IMT (p=0,04, r=0,7). By multiple linear regression analysis the relation of SHIM-5 and Med-diet score remained significant (p=0,04) after adjustment for BMI, central pulse and mean arterial pressures. We further subdivide our population according to the mean Med-diet value (28) into high and low Med-diet adherence groups. Only in the group with the greater Med-diet adherence (n=73, 60%) AIx was strongly associated to the SHIM-5 score (p=0,02) even after adjustment for PWV, age and BMI. Prolactin levels there were still related to IMT (p=0,04) after adjustment for PWV, AIx, BMI and central pulse pressure. All statistics remained significant when adjusting for ejection fraction of the left ventricle. Conclusion High adherence to the Med-diet benefits CHF hemodynamics by enforcing wave reflection amplification, thus generating a stronger pulse signal to peripheral vasculature. Moreover suppresses serum prolactin levels that relates to atheroma formation. Both actions enhance erectile performance independently of the EF of the left ventricle. It is important to advise CHF patients to adopt this dietary pattern in order to improve hemodynamic status and the sense of wellbeing.

Basis of the general theory of pathology (Part 4. "Atherosclerosis" or "Scleroatherosis"?)

This is not a play on words, but a key to solving a problem that has been deadlocked. The science of atherosclerosis is still based on the experiments of N. N. Anichkov. It always prioritizes lipid infiltration of vessel's walls. In fact, the lipid infiltration of the vessel's walls is not related to the origin of lipids in atheromas. Their origin is always associated with fatty degeneration of myofibroblasts in places of sclerosis (fibrous plaques), but not with hematogenous infiltration. The key to solving this problem lies in a disclosure of the genesis of sclerotic changes in intima. On the one hand it concerns a primary age sclerosis (compensatory) as well as secondary sclerosis (inflammatory, etc). On the other hand it is important to establish causes of degradation (fatty degeneration) and death of myofibroblasts (the so-called Langgans'cells) in places of sclerosis (fibrous plaques), followed by atheroma formation. We have first showed in vivo (at the cellular level) that a death of myofibroblasts in plaques with following release of lipids occurs due to the fact that these myofibroblasts reach the Heiflik's limit much faster than myofibroblasts on healthy vessels. These occurs due to shortening of telomeres in myofibroblasts that intensively multiply in places of reparative sclerosis. The authors propose replacing the term “atherosclerosis” with “scleroatherosis”, which more accurately reflects the essence of the disease and the sequence of events in its pathogenesis. Considering "scleroarethosis" as a nosological form, two periods of development of the process should be emphasized: the first – sclerotic period (compensatory) and the second – atheromatous (period of decompensation). The second period is accompanied by all manifestations and complications known for scleroatherosis that can't be eliminated. It is no need to spend billions on senseless "purifying” blood vessels and "lowering" cholesterol in blood plasma. It is more important to focus on a healthy lifestyle and, above all, to fight with arterial hypertension as with a main factor of blood vessels' deterioration.

Platelets and Complement Cross-Talk in Early Atherogenesis.

Atherosclerosis remains a ubiquitous and serious threat to human health. The initial formation of the atherosclerotic lesion (atheroma) is driven by pro-inflammatory signaling involving monocytes and vascular endothelial cells; later stages of the disease involve rupture of well-established atherosclerotic plaques, thrombosis, and blood vessel occlusion. While the central role of platelets in thrombosis is undisputed, platelets exhibit pro-inflammatory activities, and contribute to early-stage atheroma formation. Platelets also engage components of the complement system, an essential element of innate immunity that contributes to vascular inflammation. Here we provide an overview of the complex interplay between platelets and the complement system, with a focus on how the crosstalk between them may impact on the initiation of atheroma formation.