Endothelial Nitric Oxide Synthase (eNOS) S1176 phosphorylation status governs atherosclerotic lesion formation

Objective: We have previously demonstrated the in vivo importance of the Akt-eNOS substratekinase relationship, as defective postnatal angiogenesis characteristic of global Akt1-null mice is rescued when bred to gain-of-function eNOS S1176D mutant mice. While multiple studies support the cardioprotective role of endothelial NO generation, the causal role of Akt1-dependent eNOS S1176 phosphorylation during atherosclerotic plaque formation is not yet clear. Approach & Results: We herein bred congenic loss-of-function eNOS S1176A and gain-of function eNOS S1176D mutant mice to the proatherogenic Akt1-/-; ApoE-/- double knockout mice to definitively test the importance of Akt-mediated eNOS S1176 phosphorylation during atherogenesis. We find that a single amino acid substitution at the eNOS S1176 phosphorylation site yields divergent effects on atherosclerotic plaque formation, as an eNOS phospho-mimic aspartate (D) substitution at S1176 leads to decreased indices of atherosclerosis, even when on a proatherogenic Akt1 global deletion background. Conversely, mice harboring an unphosphorylatable mutation to alanine (S1176A) result in increased lipid deposition and cellular apoptosis, phenocopying the physiological consequence of eNOS deletion and/or impaired enzyme function. Furthermore, gene expression analyses of whole aortas indicate a combinatorial detriment from NO deficiency and Western Diet challenge, as loss-of-function eNOS SA mice on a high-fat and high-cholesterol diet present a unique expression pattern indicative of augmented T-cell activity when compared to eNOS S1176D mice. Conclusions: By using genetic epistasis approaches, we conclusively demonstrate that Akt mediated eNOS S1176 phosphorylation and subsequent activation remains to be the most physiologically relevant method of NO production to promote cardioprotective effects.

Murine roseolovirus does not accelerate amyloid-β pathology and human roseoloviruses are not over-represented in Alzheimer disease brains

Background The role of viral infection in Alzheimer Disease (AD) pathogenesis is an area of great interest in recent years. Several studies have suggested an association between the human roseoloviruses, HHV-6 and HHV-7, and AD. Amyloid-β (Aβ) plaques are a hallmark neuropathological finding of AD and were recently proposed to have an antimicrobial function in response to infection. Identifying a causative and mechanistic role of human roseoloviruses in AD has been confounded by limitations in performing in vivo studies. Recent -omics based approaches have demonstrated conflicting associations between human roseoloviruses and AD. Murine roseolovirus (MRV) is a natural murine pathogen that is highly-related to the human roseoloviruses, providing an opportunity to perform well-controlled studies of the impact of roseolovirus on Aβ deposition. Methods We utilized the 5XFAD mouse model to test whether MRV induces Aβ deposition in vivo. We also evaluated viral load and neuropathogenesis of MRV infection. To evaluate Aβ interaction with MRV, we performed electron microscopy. RNA-sequencing of a cohort of AD brains compared to control was used to investigate the association between human roseolovirus and AD. Results We found that 5XFAD mice were susceptible to MRV infection and developed neuroinflammation. Moreover, we demonstrated that Aβ interacts with viral particles in vitro and, subsequent to this interaction, can disrupt infection. Despite this, neither peripheral nor brain infection with MRV increased or accelerated Aβ plaque formation. Moreover, −omics based approaches have demonstrated conflicting associations between human roseoloviruses and AD. Our RNA-sequencing analysis of a cohort of AD brains compared to controls did not show an association between roseolovirus infection and AD. Conclusion Although MRV does infect the brain and cause transient neuroinflammation, our data do not support a role for murine or human roseoloviruses in the development of Aβ plaque formation and AD.

The scent of atherosclerosis

Vascular macrophages sense an odorant to induce atherosclerotic plaque formation

The use of the rinse aid based on a complex of natural citrus bioflavonoids for gingivitis. Clinical study

According to the Federal State Program of Primary Prevention of dental Diseases among the population of Russia in 2011 in the age group of 35–44 years, conducted by STAR, the prevalence of periodontal diseases is high – more than 80%. The high prevalence is due to the low level of oral hygiene. In addition to the standard protocol for the treatment of periodontal diseases, dentists prescribe antibacterial mouthwashes for home use. The combination of chlorhexidine 0.05% + CITROX can act as an alternative to pure chlorhexidine. This combination contributes to less plaque formation, reduces bleeding gums and has an anti-inflammatory effect. It was also noted that this rinse aid has a more pleasant taste and less pronounced side effects.

Effectiveness and safety of oral care products

The article presents the classification of the main antiseptic chemotherapeutic active substances used in personal oral care products. The efficiency and safety of active ingredients of toothpastes and rinses was analyzed. The review of literature sour-ces on the clinical effectiveness of the combination of amine fluoride with tin fluoride in the prevention of plaque formation and inflammatory processes of the oral cavity is presented.

Study of the correlation between the clinical manifestations of the inflammatory periodontal diseases and the microbiome of periodontal pathogenic microflora in young representatives of a mixed population of the European region

The age of inflammatory periodontal disease (PD) manifestations has tended to decrease over the past decades. The study of the range of periodontal pathogens in young people and their influence on the PD manifestation contributes to the predictor identification for the early prevention of this pathology.The aim was to study the correlation between the range of periodontal pathogens in the dentoalveolar sulcus/periodontal pocket (DS/PC) contents and the clinical PD manifestations in young people.We examined 28 patients (23.1 ± 0.93 years) with dental biofilm-induced gingivitis (BG), 24 patients (30.7 ± 0.6 years) with aggressive periodontitis (AgP), and 87 clinically periodontally healthy patients (21.1 ± 0.49 years) (Control). The hygiene index and the periodontal status were determined in all patients. DNA of five periodontal pathogens was identified by PCR in the DS/PC contents. The statistical analysis was performed in Statistica 13.3. The critical significance level was p ≤ 0.05.DNA was not observed in 60.9 % of the control group samples and 7.1 % of the BG group samples. In other cases, the bacteria were found separately and as part of bacterial complexes. P.g. and T.f. were most often detected in all groups. P.g. (U = 474, р < 0.01) and A.a. (U = 209, р >< 0.05) significantly contributed to the plaque formation in the control group, T.d. – in BG and AgP groups (U = 37.5, р >< 0.05 and U = 34, р >< 0.05, respectively). In the AgP group, purulent discharge was more often recorded if T.d. was detected in the PC contents (χ2 = 5.53, р >< 0.05). T.f. + P.i. and P.g. + T.f. + P.i. complexes were exclusively associated with PD. Complexes of four bacteria were found only in the AgP group. The association of periodontal pathogens and their complexes with different PD forms was revealed.>< 0.01) and A.a. (U = 209, р <0.05) significantly contributed to the plaque formation in the control group, T.d. – in BG and AgP groups (U = 37.5, р <0.05 and U = 34, р <0.05, respectively). In the AgP group, purulent discharge was more often recorded if T.d. was detected in the PC contents (χ2 = 5.53, р <0.05). T.f. + P.i. and P.g. + T.f. + P.i. complexes were exclusively associated with PD. Complexes of four bacteria were found only in the AgP group.The association of periodontal pathogens and their complexes with different PD forms was revealed.

The cellular biology of atherosclerosis with atherosclerotic lesion classification and biomarkers

Background Atherosclerosis is a chronic lipid-driven inflammatory disease with infiltration of low-density lipoprotein and is considered as the pivotal step in plaque formation. The aim of the review is to get into the fine details of pathophysiologic mechanisms responsible for atherosclerosis with atherosclerotic lesion classification. It also provides a summary of current biomarkers other than the traditional risk factors so that new treatment modalities can emerge and reduce the morbidity and mortality associated with atherosclerosis. Main body In the classification of atherosclerosis made by American Heart Association (AHA), AHA Type I lesion is the earliest vascular change described microscopically. AHA Type II lesion is primarily composed of abundant macrophages. AHA Type III lesion is the earliest of progressive lesions, while AHA Type IV lesion consists of an acellular necrotic core. Various biomarkers are implicated in different stages of the pathophysiological mechanism of plaque formation and evolution. C Reactive Protein plays a direct role in promoting the inflammatory component of atherosclerosis. Fibrinogen was demonstrated to be elevated among patients with acute thrombosis. Higher leukocyte count is associated with a greater cardiovascular risk. Cytokines have been implicated in atheroma formation and complications. High rates of protease activated receptor expression are also induced by interleukin-6 secretion in atherosclerotic lesions and areas of vascular tissue injury. Cluster of differentiation 40 receptor and its ligand have been also detected in atherosclerotic plaques. Osteopontin, acidic phosphoprotein, and osteoprotegerin have emerged as novel markers of atherosclerotic plaque composition. There are also overproductions of matrix metalloproteinases in the rupture-prone regions and promote lipid-necrotic core formation in the atherosclerotic plaque. Myeloperoxidase has been proposed as a marker of plaque instability. Oxidized low-density lipoprotein receptor 1 provides a route of entry for oxidized low-density lipoprotein into the endothelium. A human atherosclerotic lesion also expresses lipoprotein-associated phospholipase A2. Short conclusion Atherosclerotic plaques are the battlefield between an unbalanced immune response and lipid accumulation in the intima of arteries. Most of the biomarkers associated with atherosclerosis are indicators of inflammatory response and will also be used for medical purposes.

SYNTAX and Coronary Artery Calcium Score Predict Atherosclerotic Plaque Formation in the Ascending Aorta

Background: There is no study about the relationship between the complexity of coronary artery disease (SYNTAX SCORE; SS), and coronary artery calcium (CAC) score, accompanied with aortic calcium score (ACS) levels. The objective of this study was to investigate the relationship between the preoperative SS and CAC scores accompanying ACS in isolated CABG patients and their postoperative clinical results. Methods: This study included 130 consecutive CABG patients. The mean age of the patients was 62.3 ± 8.62 years (range: 47-84 years). SS was measured using coronary angiography by an experienced cardiologist. We investigated the ACS accompanied with CAC scores using a multidetector computed tomography (MDCT) in the same session, preoperatively. Measurements of the CAC score and ACS were measured by an experienced radiologist, who was unaware of the study in the same session. In order to investigate aortic wall pathology in patients with positive aortic calcification, we provided aortic tissue samples prior to the proximal anastomosis of bypass grafts using No:11 scalpel. Results: Overall median SS was 39 ± 7.2 (range: 15-41). CAC score was zero in 34 patients (26.1%). For the patients with a CAC score of zero, the median SS was 32 ± 9.4. There was no evidence of aortic calcification or plaque formation in 62 patients (47.6%). In these patients, the median SS was 35.6 ± 11.3. No significant difference was found when both groups were compared and for those patients with a calcific score of zero (P = .85). The median CAC score and ACS were 238 ± 122 AU (range: 0-1238 AU) and 112 ± 40 AU (range: 0-730 AU), respectively (P = .0033). For patients with a CAC score and ACS ≥400 AU, the mean SYNTAX score was ≥ 37. SS was correlated with CAC score (R:0.585; P < .0001). SYNTAX was correlated with ACS (R:0.557; P < .001). In multivariate analysis of SS (OR 1.053, 95% CI: 1.003–1.106, P = .039), gender (OR 0.189, 95% CI: 0.053–0.678, P = 0.011), age (OR 1.454, 95% CI: 1.256–1.632, P = .012), and diabetes mellitus (OR 0.341, 95% CI: 1.006–1.124, P = .014) were independent predictors for CAC score and aortic calcification. Conclusions: CAC score and ACS are strongly correlated with the complexity of coronary arteries in CABG patients. The total CAC score (≥ 400 AU) was independently associated with the degree of SS (>37). To prevent MACCE and mortality in CABG patients, we suggest the measurement of CAC score accompanied with ACS using MDCT as a non-invasive method. Highlight points: • Atherosclerotic plaque formation in aorta and coronary arteries are the main risk factors for stroke and infarction in CABG operations. •SYNTAX score value and aortic atherosclerosis levels are directly correlated. •SYNTAX score may predict the complications due to atherosclerosis during heart surgery.