Sortilin as a marker of atherosclerosis: biological and pathophysiological aspects

Subclinical atherosclerosis is an independent predictor of increased cardiovascular risk, including patients with hypertension. The article provides an overview of the pathogenetic role in atherogenesis and cardiovascular risk stratification of sortilin peptide which belongs to the family of vacuolar sorting receptors of type I. Circulating sortilin impacts both lipid and non-lipid pathogenetic mechanisms of atherogenesis. It can serve as an early biomarker of cardiovascular risk and a potential therapeutic target for dyslipidemia management and atherosclerosis at subclinical level.

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A Mutation in the Protein S Pseudogene Is Linked to Protein S Deficiency in a Thrombophilic Family

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651024 ◽

1989 ◽

Vol 62 (03) ◽

pp. 897-901 ◽

Cited By ~ 10

Author(s):

Hans K Ploos van Amstel ◽

Pieter H Reitsma ◽

Karly Hamulyák ◽

Christine E M de Die-Smulders ◽

Pier M Mannucci ◽

...

Keyword(s):

Total Protein ◽

Protein S ◽

Southern Analysis ◽

Type I ◽

Protein S Deficiency ◽

S Deficiency ◽

The Family ◽

Dna Pattern ◽

Deficiency Type ◽

S Genes

SummaryProbands from 15 unrelated families with hereditary protein S deficiency type I, that is having a plasma total protein S concentration fifty percent of normal, were screened for abnormalities in their protein S genes by Southern analysis. Two probands were found to have a deviating DNA pattern with the restriction enzyme Mspl. In the two patients the alteration concerned the disappearance of a Mspl restriction site, CCGG, giving rise to an additional hybridizing Mspl fragment.Analysis of relatives of both probands showed that in one family the mutation does not co-segregate with the phenotype of reduced plasma protein S. In the family of the other proband, however, complete linkage between the mutated gene pattern and the reduced total protein S concentration was found: 12 heterozygous relatives showed the additional Mspl fragment but none of the investigated 26 normal members of the family. The mutation is shown to reside in the PSβ gene, the inactive protein S gene. The cause of type I protein S deficiency, a defect PSα gene has escaped detection by Southern analysis. No recombination has occurred between the PSα gene and the PSβ gene in 23 informative meioses. This suggests that the two protein S genes, located near the centromere of chromosome 3, are within 4 centiMorgan of each other.

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CARDIOVASCULAR RISK FACTORS PECULIARITIES IN MEN UNDER 60 YEARS OLD WITH MYOCARDIAL INFARCTION AND CHRONIC INFLAMMATORY LUNG DISEASES

"Medical & pharmaceutical journal "Pulse" ◽

10.26787/nydha-2686-6838-2020-22-9-21-25 ◽

2020 ◽

pp. 21-25

Author(s):

Tupitsyn V.V. ◽

Bataev Kh.M. ◽

Men’shikova A.N. ◽

Godina Z.N.

Keyword(s):

Risk Factors ◽

Myocardial Infarction ◽

Heart Disease ◽

Cardiovascular Risk ◽

Digestive System ◽

Control Group ◽

Study Group ◽

Type I ◽

Internal Organs ◽

History Of

Relevance. Information about the cardiovascular diseases risk factors (CVD RF) for in men with chronic lung inflam-matory pathology (CLID) is contradictory and requires clarification. Aim. To evaluate the peculiarities of CVD RF in men under 60 years of age with CLID in myocardial infarction (MI) to improve prevention. Material and methods. The study included men aged 19-60 years old with type I myocardial infarction. Patients are divided into two age-comparable groups: I - the study group, with CLID - 142 patients; II - control, without it - 424 patients. A comparative analysis of the frequency of observation of the main and additional cardiovascular risk fac-tors in groups was performed. Results. In patients of the study group, more often than in the control group we observed: hereditary burden of is-chemic heart disease (40.8 and 31.6%, respectively; p = 0.0461) and arterial hypertension (54.2 and 44.6%; p = 0.0461), frequent colds (24.6 and 12.0%; p = 0.0003), a history of extrasystoles (19.7 and 12.7%; p = 0.04); chronic foci of infections of internal organs (75.4 and 29.5%; p˂0.0001), non-ulcer lesions of the digestive system (26.1 and 14.6%; p = 0.007), smoking (95.1 and 66.3%; p˂0.0001), MI in winter (40.8 and 25.9%; p = 0.006). Less commonly were observed: oral cavity infections (9.2 and 23.6%; p˂0.0001); hypodynamia (74.5 and 82.5%; p = 0.0358), over-weight (44.4 and 55.2%; p = 0.0136), a subjective relationship between the worsening of the course of coronary heart disease and the season of the year (43.7 and 55.2%; p = 0.0173) and MI - in the autumn (14.1 and 21.9%; p = 0.006) period. Conclusions. The structure of CVD RF in men under 60 years of age with CLID with MI is characterized by the pre-dominance of smoking, non-ulcer pathology of the digestive system, frequent pro-student diseases, meteorological dependence, a history of cardiac arrhythmias and foci of internal organ infections. It is advisable to use the listed factors when planning preventive measures in such patients.

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Type I Interferon as cardiovascular risk factor in systemic and cutaneous lupus erytheematosus: A systematic review

Autoimmunity Reviews ◽

10.1016/j.autrev.2021.102794 ◽

2021 ◽

pp. 102794

Author(s):

Chiara Kirchler ◽

Emma Husar-Memmer ◽

Klemens Rappersberger ◽

Kylie Thaler ◽

Ruth Fritsch-Stork

Keyword(s):

Systematic Review ◽

Risk Factor ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factor ◽

Type I Interferon ◽

Type I ◽

Cutaneous Lupus

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POS0586 RHEUMATOID ARTHRITIS IS AN INFLAMMATORY DISEASE WITH A HIGH CARDIOVASCULAR RISK

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.4080 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 526.1-526

Author(s):

L. Nacef ◽

H. Riahi ◽

Y. Mabrouk ◽

H. Ferjani ◽

K. Maatallah ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Risk Factors ◽

Cardiovascular Risk ◽

Carotid Artery ◽

Internal Carotid ◽

Subclinical Atherosclerosis ◽

External Carotid ◽

Significant Difference ◽

The Mean ◽

The Right

Background:Hypertension, diabetes, and dyslipidemia are traditional risk factors of cardiac events. Carotid ultrasonography is an available way to detect subclinical atherosclerosis.Objectives:This study aimed to compare the intima-media thickness in RA patients based on their personal cardiovascular (CV) history of hypertension (hypertension), diabetes, and dyslipidemia.Methods:The present study is a prospective study conducted on Tunisian RA patients in the rheumatology department of Mohamed Kassab University Hospital (March and December 2020). The characteristics of the patients and those of the disease were collected.The high-resolution B-mode carotid US measured the IMT, according to American Society of Echocardiography guidelines. The carotid bulb below its bifurcation and the internal and external carotid arteries were evaluated bilaterally with grayscale, spectral, and color Doppler ultrasonography using proprietary software for carotid artery measurements. IMT was measured using the two inner layers of the common carotid artery, and an increased IMT was defined as ≥0.9 mm. A Framingham score was calculated to predict the cardiovascular risk at 10-year.Results:Forty-seven patients were collected, 78.7% of whom were women. The mean age was 52.5 ±11.06 [32-76]. The rheumatoid factor (RF) was positive in 57.8% of cases, and anti-citrullinated peptide antibodies (ACPA) were positive in 62.2% of cases. RA was erosive in 81.6% of cases. Hypertension (hypertension) was present in 14.9% of patients, diabetes in 12.8% of patients, and dyslipidemia in 12.8% of patients. Nine patients were active smokers. The mean IMT in the left common carotid (LCC) was 0.069 ±0.015, in the left internal carotid (LIC) was 0.069 ±0.015, in the left external carotid (LEC) was 0.060 ±0.023. The mean IMT was 0.068 ±0.01 in the right common carotid (RCC), 0.062 ±0.02 in the right internal carotid (RIC), and 0.060 ±0.016 in the right external carotid (REC). The IMT was significantly higher in the left common carotid (LCC) in patients with hypertension (p=0.025). There was no significant difference in the other ultrasound sites (LIC, LEC, RCC, RIC, and REC) according to the presence or absence of hypertension. The IMT was also significantly increased in patients with diabetes at LCC (p=0.017) and RIC (p=0.025). There was no significant difference in the IMT at different ultrasound sites between patients with and without dyslipidemia.Conclusion:Hypertension was significantly associated with the increase in IMT at the LCC level in RA patients. Diabetes had an impact on IMT in LCC and RIC. However, dyslipidemia did not affect the IMT at the different ultrasound sites.References:[1]S. Gunter and al. Arterial wave reflection and subclinical atherosclerosis in rheumatoid arthritis. Clinical and Experimental Rheumatology 2018; 36: Clinical E.xperimental.[2]Aslan and al. Assessment of local carotid stiffness in seronegative and seropositive rheumatoid arthritis. SCANDINAVIAN CARDIOVASCULAR JOURNAL, 2017.[3]Martin I. Wah-Suarez and al, Carotid ultrasound findings in rheumatoid arthritis and control subjects: A case-control study. Int J Rheum Dis. 2018;1–7.[4]Gobbic C and al. Marcadores subclínicos de aterosclerosis y factores de riesgo cardiovascular en artritis temprana. Subclinical markers of atherosclerosis and cardiovascular risk factors in early arthritis marcadores subclínicos de aterosclerose e fatores de risco cardiovascular na artrite precoce.Disclosure of Interests:None declared

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Meta-analysis of epigenome-wide association studies of carotid intima-media thickness

European Journal of Epidemiology ◽

10.1007/s10654-021-00759-z ◽

2021 ◽

Author(s):

Eliana Portilla-Fernández ◽

Shih-Jen Hwang ◽

Rory Wilson ◽

Jane Maddock ◽

W. David Hill ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Dna Methylation ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factors ◽

Association Studies ◽

Subclinical Atherosclerosis ◽

Intima Media Thickness ◽

Carotid Intima Media Thickness ◽

Media Thickness

AbstractCommon carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta = −0.0264, p value = 3.5 × 10–8) in the discovery panel and was replicated in replication panel (beta = −0.07, p value = 0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value = 1.4 × 10–13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.

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N6-methyladenosine RNA modification suppresses antiviral innate sensing pathways via reshaping double-stranded RNA

Nature Communications ◽

10.1038/s41467-021-21904-y ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Weinan Qiu ◽

Qingyang Zhang ◽

Rui Zhang ◽

Yangxu Lu ◽

Xin Wang ◽

...

Keyword(s):

Rna Virus ◽

Negative Regulator ◽

Rna Modification ◽

Type I ◽

Viral Immunity ◽

Potential Therapeutic Target ◽

Viral Dsrna ◽

Double Stranded Rna ◽

Genetic Ablation ◽

Vesicular Stomatitis

AbstractDouble-stranded RNA (dsRNA) is a virus-encoded signature capable of triggering intracellular Rig-like receptors (RLR) to activate antiviral signaling, but whether intercellular dsRNA structural reshaping mediated by the N6-methyladenosine (m6A) modification modulates this process remains largely unknown. Here, we show that, in response to infection by the RNA virus Vesicular Stomatitis Virus (VSV), the m6A methyltransferase METTL3 translocates into the cytoplasm to increase m6A modification on virus-derived transcripts and decrease viral dsRNA formation, thereby reducing virus-sensing efficacy by RLRs such as RIG-I and MDA5 and dampening antiviral immune signaling. Meanwhile, the genetic ablation of METTL3 in monocyte or hepatocyte causes enhanced type I IFN expression and accelerates VSV clearance. Our findings thus implicate METTL3-mediated m6A RNA modification on viral RNAs as a negative regulator for innate sensing pathways of dsRNA, and also hint METTL3 as a potential therapeutic target for the modulation of anti-viral immunity.

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Cardiovascular Calcification as a Marker of Increased Cardiovascular Risk and a Surrogate for Subclinical Atherosclerosis: Role of Echocardiography

Journal of Clinical Medicine ◽

10.3390/jcm10081668 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1668

Author(s):

Andrea Faggiano ◽

Gloria Santangelo ◽

Stefano Carugo ◽

Gregg Pressman ◽

Eugenio Picano ◽

...

Keyword(s):

Cardiovascular Risk ◽

Cardiovascular Events ◽

Cardiac Computed Tomography ◽

Subclinical Atherosclerosis ◽

Organ Damage ◽

Conventional Risk Factor ◽

Promising Tool ◽

Ultrasound Evaluation ◽

The Individual ◽

Mitral Apparatus

The risk prediction of future cardiovascular events is mainly based on conventional risk factor assessment by validated algorithms, such as the Framingham Risk Score, the Pooled Cohort Equations and the European SCORE Risk Charts. The identification of subclinical atherosclerosis has emerged as a promising tool to refine the individual cardiovascular risk identified by these models, to prognostic stratify asymptomatic individuals and to implement preventive strategies. Several imaging modalities have been proposed for the identification of subclinical organ damage, the main ones being coronary artery calcification scanning by cardiac computed tomography and the two-dimensional ultrasound evaluation of carotid arteries. In this context, echocardiography offers an assessment of cardiac calcifications at different sites, such as the mitral apparatus (including annulus, leaflets and papillary muscles), aortic valve and ascending aorta, findings that are associated with the clinical manifestation of atherosclerotic disease and are predictive of future cardiovascular events. The aim of this paper is to summarize the available evidence on clinical implications of cardiac calcification, review studies that propose semiquantitative ultrasound assessments of cardiac calcifications and evaluate the potential of ultrasound calcium scores for risk stratification and prevention of clinical events.

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AB0258 CAROTID INTIMA-MEDIA THICKNESS AND SERUM BIOMARKERS IN PARAGUAYAN PATIENTS WITH RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.6520 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1428.2-1428

Author(s):

V. Valinotti ◽

A. Paats ◽

R. Acosta ◽

L. Roman ◽

I. Acosta-Colman ◽

...

Keyword(s):

Cardiovascular Risk ◽

Disease Duration ◽

Subclinical Atherosclerosis ◽

High Sensitivity ◽

Intima Media Thickness ◽

Carotid Intima Media Thickness ◽

Serum Biomarkers ◽

Carotid Plaques ◽

Media Thickness ◽

Hs Crp

Background:The mechanism of increased cardiovascular risk in RA is not well understood and is independent of traditional CV risk factors. Intima-media thickness of the common carotid wall measured by ultrasonogram is a safe and useful biomarker of early stage atherosclerosis that correlates with coronary involvement; and it correlates with severity and duration of disease. Several studies have shown a relationship between inflammation markers, endothelial dysfunction markers, and carotid involvement. (1)Objectives:To determine the presence of inflammation biomarkers and its relationship with subclinical atherosclerosis measured by carotid ultrasound, and with the clinical characteristics in patients with established Rheumatoid Arthritis (RA)Methods:Descriptive, cross sectional, prospective study, in a Paraguayan cohort of patients with RA meeting ACR/EULAR2010 criteria. This study had two phases: the first one, included a standardized questionnaire according to the variables included in the Cardiovascular Risk project (PINV15-0346), from the National Sciences and Technology Council (CONACYT), and physical examination; the second one included laboratory sample collection performed by a specialized laboratory for serum biomarkers measurement for cardiovascular risk prediction (i.e endothelin, alpha-TNF, E-selectin, homocysteine, apolipoprotein, fibrinogen, and high sensitivity-CRP levels) and carotid ultrasound evaluation by a trained specialist, to evaluate subclinical atherosclerosis. Subclinical atherosclerosis was defined as carotid intima-media thickness (CIMT) >0,9mm and/or presence of carotid plaques. All patients signed informed consent. SPSS 23rd version was used for data analysis. Quantitative variables were presented as means and qualitative as frequencies. Chi square test was performed for comparisons between dichotomous variables and t Student for continuous, and p ≤ 0.05 for statistical significance.Results:100 patients were included, 87% were women, mean disease duration 130.9±102.64 months, 77% were RF positive, and 84.4% were ACPA positive, 43.4% had bone erosions, mean ESR-DAS28 was 3,42±1,1; 30% had remission criteria. 39% had extra-articular manifestations.Elevated serum biomarkers were found: fibrinogen >400 mg/dL 88.2%, high sensitivity-CRP (hs-CRP) >5mg/dL 42.9%, endothelin >2 ng/mL 20%, alpha-TNF >15,6 pg/mL 13.1%, E-selectin >79,2 ng/mL 6%. 25.3% had CIMT >0,9 mm and mean CIMT was 0.68±0.25mm. 27.14% had carotid plaques. Patients with CIMT>1mm had higher frequency of family history of arterial hypertension (p=0.006), greater mean disease duration (p=0.0007), hip circumference (p=0.014), blood pressure (SBP p=0.038, DBP p=0.027), HAQ levels (p=0,019) and hs-CRP levels (p=0.013), also lower mean height (p=0,04); while carotid plaques were related to higher homocysteine (p=0.026) and hs-CRP levels (p=0.024).Conclusion:A considerable percentage of patients had subclinical atherosclerosis. Patients with CIMT>0,9mm had a longer disease duration, higher HAQ levels, hip circumference, as well as higher BP. High levels of hs-CRP were more frequently related to the presence of subclinical atherosclerosisReferences:[1]Aday, A. targeting residual inflammatory risk: a shifting paradigm for atherosclerotic disease. Frontiers in cardiovascular medicine. 2019. 6:16.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403155/pdf/fcvm-06-00016.pdfDisclosure of Interests:None declared

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Association between parents’ socioeconomic conditions and nutritional status during childhood and the risk of cardiovascular disease in their adult offspring: an intergenerational study in south India

Journal of Epidemiology & Community Health ◽

10.1136/jech-2020-216261 ◽

2021 ◽

pp. jech-2020-216261

Author(s):

Poppy Alice Carson Mallinson ◽

Bharati Kulkarni ◽

Santhi Bhogadi ◽

Sanjay Kinra

Keyword(s):

Cardiovascular Disease ◽

Cardiovascular Risk ◽

Maternal Nutrition ◽

Subclinical Atherosclerosis ◽

Intima Media Thickness ◽

Epidemiological Data ◽

Adult Offspring ◽

Inverse Association ◽

Socioeconomic Conditions ◽

Leg Length

BackgroundSome researchers have suggested that parents’ exposure to poor socioeconomic conditions during childhood can increase their offspring’s risk of cardiovascular disease, primarily through poor maternal nutrition and growth. However, epidemiological data on this association are limited. In an intergenerational cohort from rural India, we examined the association of parental childhood socioeconomic conditions and stature with offspring’s cardiovascular risk, hypothesising an inverse association between the two.MethodsWe analysed data on 3175 adult offspring (aged 18–35 years, 58% men) and their parents from the third wave of the Andhra Pradesh Children and Parents’ Study (2010–12). We used multilevel linear regression to estimate the association of parents’ Standard of Living Index (SLI, an asset-based measure of socioeconomic conditions) in childhood, height and leg length with subclinical atherosclerosis and cardiovascular risk factors in their offspring.ResultsIn multivariable models adjusted for offspring’s socioeconomic conditions in childhood and adulthood, associations (beta coefficients and 95% CIs) of mother’s and father’s childhood SLI (per SD) were −0.00 mm (−0.01, 0.01) and 0.01 mm (−0.00, 0.02) for carotid intima media thickness, −0.17 mm Hg (−0.61, 0.27) and −0.30 mm Hg (−0.78, 0.20) for systolic blood pressure, −0.43 mg/dL (−2.00, 1.15) and −1.07 mg/dL (−2.79, 0.65) for total cholesterol and −0.00mU/L (−0.04, 0.03) and 0.01mU/L (−0.03, 0.04) for log fasting insulin. Results were of similar magnitude for parental height and leg length.ConclusionsOur findings do not support an inverse association between parental childhood socioeconomic conditions or stature and offspring’s risk of cardiovascular disease. Intergenerational socioeconomic influences on cardiovascular risk may be of limited public health significance for this setting.

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