scholarly journals The Clinical and Vascular Characteristics of RNF213 c.14576G>A Variant-Related Intracranial Major Artery Disease in China

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Weiyang Cheng ◽  
Sufang Xue ◽  
Fang Wu ◽  
Xiaowei Song ◽  
Qiang Huang ◽  
...  
Keyword(s):  
Ring Finger ◽  
Image Data ◽  
Chinese Patients ◽  
Outer Diameter ◽  
Ring Finger Protein ◽  
Collateral Vessel ◽  
Intracranial Atherosclerotic Disease ◽  
Significant Difference ◽  
Artery Disease ◽  
Collateral Vessels

Background and Purpose. Recently, several studies indicated the c.14576G>A variant on the ring finger protein 213 (RNF213), a founder variant of moyamoya diseases (MMD), was associated with non-MMD intracranial major artery stenosis/occlusion (non-MMD ICASO). We proposed that RNF213 variant-related ICASO including MMD might be a special entity with its own characteristics based on a genetic background. The aim of the study was to learn the clinical and vascular features of RNF213 variant-related ICASO. Moreover, we tried to explore the clinical significance of a testing variant in ICASO patients in China. Methods. Clinical material and routine image data were collected in 160 Chinese patients with ICASO, including 41 verified MMD and 119 non-MMD. DNA samples were extracted, and the c.14576G>A variant on RNF213 was genotyped. Then, the clinical and vascular features were compared between the patients with and without a relevant variant. Furthermore, the patients with RNF213 mutation were performed with high resolution magnetic resonance imaging (HR-MRI) examination to conclude features of the artery wall. Results. There were 16 (10%) patients (including 9 MMD and 7 non-MMD ICASO) presenting a heterozygous c.14576G>A variant while none of homozygote was found. Compared to the patients without the c.14576G>A variant, the variant group had more female, less symptomatic patients, and more possibility of having collateral vessels in vascular imaging. In the symptomatic subgroup, there is no significant difference in clinical presentation (p>0.05) between two groups. However, RNF213 variant-related ICASO had lower scores in NIHSS (1.0±3.0 vs. 3.9±5.0, p<0.05) but not in mRS. In the symptomatic subgroup, in addition, most of the HR-MRI images of variant ICASO (77.8%, 7 of 9) were characterized by a shrunken outer diameter, concentric thickening vessel wall, and collateral vessel structures on the stenotic portion, which was prone to be diagnosed as HR-MMD (a MMD diagnosis diagnosed by HR-MRI). The rest of the two variants showed a relatively eccentric luminal narrow, normal outer diameter without collateral vessel findings, identified as HR-ICAD (intracranial atherosclerotic disease diagnosed by HR-MRI). Conclusions. Our study demonstrated that the c.14576G>A variant on RNF213 may be a biomarker to good outcome of ICASO in Chinese. The variant-related ICASO was characterized by both features of MMD and ICAD diagnosed by HR-MRI.

scholarly journals The Peripubertal Decline in Makorin Ring Finger Protein 3 Expression is Independent of Leptin Action

2020 ◽  
Vol 4 (7) ◽  
Author(s):  
Stephanie A Roberts ◽  
Ana Paula Abreu ◽  
Victor M Navarro ◽  
Joy N Liang ◽  
Caroline A Maguire ◽  
...  
Keyword(s):  
Arcuate Nucleus ◽  
Pubertal Development ◽  
Ring Finger ◽  
Central Precocious Puberty ◽  
Mrna Levels ◽  
Ring Finger Protein ◽  
Loss Of Function ◽  
Wild Type ◽  
Finger Protein ◽  
Significant Difference

Abstract A critical body weight is necessary for pubertal development, an effect mediated in part by leptin. The potential regulation by leptin of Makorin Ring Finger Protein 3 (MKRN3), in which loss-of-function mutations are the most common genetic cause of central precocious puberty, has not been previously explored. In mice, expression of Mkrn3 in the hypothalamic arcuate nucleus is high early in life and declines before the onset of puberty. Therefore, we aimed to explore if leptin contributes to the decrease in hypothalamic Mkrn3 mRNA levels observed in mice during pubertal development. We first used a leptin-deficient (ob/ob) mouse model. Mkrn3 mRNA levels in the mediobasal hypothalamus (MBH), which includes the arcuate nucleus, and in the preoptic area (POA), both showed a significant decrease with age from postnatal day (PND) 12 to PND30 in ob/ob mice in both males and females, similar to that observed in wild-type mice. To further explore the effects of leptin on Mkrn3 expression, we exposed prepubertal wild-type mice to high levels of leptin from age PND9-12, which did not result in any significant difference in Mkrn3 expression levels in either the MBH or POA. In summary, regulation of Mkrn3 expression by leptin was not observed in either the MBH or the POA, 2 hypothalamic sites important for pubertal maturation. These data suggest that the decline in Mkrn3 at the onset of puberty may occur independently of leptin and support our hypothesis that MKRN3 is a bona fide controller of puberty initiation.

Increased incidence and treatment of intracranial atherosclerotic disease during mechanical thrombectomy is safe, even with an increased number of passes

2021 ◽  
pp. neurintsurg-2020-017114
Author(s):  
Marlon Carl Monayao ◽  
Ahmed A Malik ◽  
Laurie Preston ◽  
Marlon Carl Monayao Sr ◽  
Wondwossen Tekle ◽  
...  
Keyword(s):  
Mechanical Thrombectomy ◽  
Atherosclerotic Disease ◽  
Vessel Occlusion ◽  
Intracranial Atherosclerotic Disease ◽  
Significant Difference ◽  
Artery Disease ◽  
Comprehensive Stroke Center ◽  
Stroke Center ◽  
Angioplasty And Stenting ◽  
Number Of Passes

BackgroundThe incidence of intracranial atherosclerotic disease (ICAD) in acute ischemic stroke treated with mechanical thrombectomy (MT) is not well defined, and its description may lead to improved stroke devices and rates of first pass success.MethodsA retrospective study was performed on MT patients from 2012 to 2019 at a comprehensive stroke center using chart review and angiogram analysis. Angiograms at the time of MT were reviewed for ICAD, and location and severity were recorded. Patients with ICAD were divided according to ICAD location relative to the large vessel occlusion (LVO) site. Statistical analyses were performed on baseline demographics, comorbidities, MT procedure variables, outcome variables, and their association with ICAD.ResultsOf the 533 patients (mean age 70.4 (SD 13.20) years, 43.5% women), 131 (24.6%) had ICAD. There was no significant difference in favorable discharge outcomes (modified Rankin Scale score of 0–2; 23.8% ICAD vs 27.0% non-ICAD; p=0.82) or groin puncture to recanalization times (average 43.5 (range 8–181) min for ICAD vs 40.2 (4–204) min for non-ICAD; p=0.42). Patients with ICAD experienced a significantly higher number of passes (average 1.8 (range 1–7) passes for ICAD vs 1.6 (1–5) passes for non-ICAD; p=0.0059). Adjusting for age, ≥3 device passes, baseline National Institutes of Health Stroke Scale, rates of angioplasty only, rates of concurrent angioplasty and stenting, coronary artery disease and atrial fibrillation incidences, and time from emergency department arrival to recanalization, yielded no significant difference in rates of favorable outcomes between the two groups.ConclusionPatients who underwent MT with underlying ICAD had similar rates of favorable outcomes as those without, but required a higher number of device passes.

scholarly journals Predictive role of heterozygous p.R4810K of RNF213 in the phenotype of Chinese moyamoya disease

Neurology ◽  
2020 ◽  
Vol 94 (7) ◽  
pp. e678-e686 ◽  
Author(s):  
Yue Wang ◽  
Zhengshan Zhang ◽  
Ling Wei ◽  
Qian Zhang ◽  
Zhengxing Zou ◽  
...  
Keyword(s):  
Moyamoya Disease ◽  
Ring Finger ◽  
Severe Form ◽  
Chinese Patients ◽  
Onset Age ◽  
Ring Finger Protein ◽  
Coastal Cities ◽  
Predictive Role ◽  
Control Study

ObjectivePrecise genetic analyses were conducted with ring finger protein 213 (RNF213) in relation to a particular clinical phenotype in Chinese patients with moyamoya disease (MMD) to determine whether heterozygosity is responsible for the early-onset and severe form of this disease.MethodsA case–control study for RNF213 p.R4810K involving 1,385 Chinese patients with MMD and 2,903 normal control participants was performed. Correlation analyses between genotype and phenotype or different clinical features were also statistically explored.ResultsAn obvious trend was observed: the carrying rate of RNF213 p.R4810K gradually decreased when moving from coastal cities in northeast, north, and east China to southern cities or inland areas. Higher frequencies of p.R4810K were observed in patients with MMD compared with control participants (odds ratio, 48.1; 95% confidence interval, 29.1–79.6; p = 1.6 × 10−141). In addition, the onset age of all patients with the GA and AA genotypes were lower than with the GG genotype, and the median onset age was 40.0, 36.0, and 11.5 years with GG, GA, and AA, respectively, thereby confirming that those with GA or AA could acquire MMD during early life stages. Patients with MMD with the GA genotype were more susceptible to posterior cerebral artery (PCA) involvement compared to those with the GG genotype (38.4% vs 23.3%, p = 8.3 × 10−7).ConclusionsStrong evidence suggests that the carrying rate of RNF213 p.R4810K is closely related MMD risk in China and has given rise to an earlier onset age and more severe PCA involvement.

Markers of Hemostatic Activation in Affected Coronary Arteries during Angioplasty

1994 ◽  
Vol 72 (05) ◽  
pp. 672-675 ◽  
Author(s):  
Nicolas W Shammas ◽  
Michael J Cunningham ◽  
Richard M Pomearntz ◽  
Charles W Francis
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Venous Blood ◽  
Balloon Inflation ◽  
Blood Samples ◽  
Hemostatic System ◽  
Significant Difference ◽  
Hemostatic Markers ◽  
Artery Disease ◽  
High Doses

SummaryTo characterize the extent of early activation of the hemostatic system following angioplasty, we obtained blood samples from the involved coronary artery of 11 stable angina patients during the procedure and measured sensitive markers of thrombin formation (fibrino-peptide A, prothrombin fragment 1.2, and soluble fibrin) and of platelet activation ((3-thromboglobulin). Levels of hemostatic markers in venous blood obtained from 14 young individuals with low pretest probability for coronary artery disease were not significantly different from levels in venous blood or intracoronary samples obtained prior to angioplasty. Also, there was no translesional (proximal and distal to the lesion) gradient in any of the hemostatic markers before or after angioplasty in samples obtained between 18 and 21 min from the onset of the first balloon inflation. Furthermore, no significant difference was noted between angioplasty and postangioplasty intracoronary concentrations. We conclude that intracoronary hemostatic activation does not occur in the majority of patients during and immediately following coronary angioplasty when high doses of heparin and aspirin are administered.

The Effect of Antiplatelet Drugs on Plasma Betathromboglobulin in Coronary Artery Disease

1979 ◽  
Author(s):  
P Han ◽  
A Turpie ◽  
E Genton ◽  
M Gent
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Crossover Trial ◽  
Specific Protein ◽  
Antiplatelet Drugs ◽  
Significant Difference ◽  
Pre Treatment ◽  
Artery Disease ◽  
Therapeutic Doses ◽  
Granule Release

Platelets play a role in the development and complications of coronary artery disease (CAD) and a number of abnormalities of platelet function which can be corrected by antiplatelet drugs have been described. Betathromboglobulin (BTG), a platelet-specific protein which is released from α-granules during platelet activation is significantly elevated in patients with angiographically demonstrated CAD (51.0 ± 31.0 ng/ml., n = 50) compared to normal (28.0 ± 8.0 ng/ml., n = 70) p < 0.001. The effect of sulphinpyrazone (800 mg.) or aspirin (1200 mg.)/dipyridamole (200 mg.) on plasma BTG in CAD was studied in a blind prospective crossover trial in 25 patients. Mean BTG concentration pre-treatment was 52.3 ng/ml. and after 1 month’s treatment with placebo, sulphinpyrazone or aspirin/dipyridamole mean plasma BTG concentrations were 53.5, 49.6 and 56.7 ng/ml. respectively. Analysis of variance showed no significant difference between the means (p > 0.1) . This study confirms increased plasma BTG concentrations in patients with CAD and indicates that therapeutic doses of these antiplatelet drugs do not significantly effect the BTG level and thus appear not to prevent α-granule release in CAD.

Osteoprotegerin and Osteopontin Serum Levels are Associated with Vascular Function and Inflammation in Coronary Artery Disease Patients

2020 ◽  
Vol 18 (5) ◽  
pp. 523-530 ◽  
Author(s):  
Konstantinos Maniatis ◽  
Gerasimos Siasos ◽  
Evangelos Oikonomou ◽  
Manolis Vavuranakis ◽  
Marina Zaromytidou ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Endothelial Function ◽  
Vascular Function ◽  
Serum Levels ◽  
Atherosclerosis Progression ◽  
Control Subjects ◽  
Significant Difference ◽  
Artery Disease ◽  
Stable Cad

Background: Osteoprotegerin and osteopontin have recently emerged as key factors in both vascular remodelling and atherosclerosis progression. Interleukin-6 (IL-6) is an inflammatory cytokine with a key role in atherosclerosis. The relationship of osteoprotegerin, osteopontin, and IL-6 serum levels with endothelial function and arterial stiffness was evaluated in patients with coronary artery disease (CAD). Methods: We enrolled 219 patients with stable CAD and 112 control subjects. Osteoprotegerin, osteopontin and IL-6 serum levels were measured using an ELISA assay. Endothelial function was evaluated by flow-mediated dilation (FMD) in the brachial artery and carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness. Results: There was no significant difference between control subjects and CAD patients according to age and sex. Compared with control subjects, CAD patients had significantly impaired FMD (p<0.001) and increased PWV (p=0.009). CAD patients also had significantly higher levels of osteoprotegerin (p<0.001), osteopontin (p<0.001) and IL-6 (p=0.03), compared with control subjects. Moreover, IL-6 levels were correlated with osteoprotegerin (r=0.17, p=0.01) and osteopontin (r=0.30, p<0.001) levels. FMD was correlated with osteoprotegerin levels independent of possible confounders [b coefficient= - 0.79, 95% CI (-1.54, -0.05), p=0.04]. Conclusion: CAD patients have increased osteoprotegerin, osteopontin and IL-6 levels. Moreover, there is a consistent association between osteoprotegerin and osteopontin serum levels, vascular function and inflammation in CAD patients. These findings suggest another possible mechanism linking osteoprotegerin and osteopontin serum levels with CAD progression through arterial wall stiffening and inflammation.

HIV may indirectly accelerate coronary artery disease through enhancing the effects of conventional and non-conventional cardiovascular risk factors

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Kolossvary ◽  
E.K Fishman ◽  
G Gerstenblith ◽  
D.A Bluemke ◽  
R.N Mandler ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Hiv Infection ◽  
Cardiovascular Risk Factors ◽  
Agatston Score ◽  
Funding Source ◽  
Significant Difference ◽  
Ascvd Risk ◽  
Artery Disease

Abstract Background/Introduction Cross-sectional studies are inconsistent on the potential independent adverse effects of human immunodeficiency virus (HIV)-infection on coronary artery disease (CAD). Furthermore, there is no information on the potential effects of HIV-infection on plaque volumes. Also, only the independent effects of HIV-infection on CAD have been investigated. Purpose In a prospective longitudinal observational cohort, we wished to assess whether HIV-infection accelerates CAD independently, or by acting in synergistic fashion with conventional and nonconventional cardiovascular risk factors to accelerate disease progression as assessed by clinical and volumetric parameters of CAD on coronary CT angiography (CCTA). Methods Overall, 300 asymptomatic individuals without cardiovascular symptoms but with CCTA-confirmed coronary plaques (210 males, age: 48.0±7.2 years) with or without HIV (226 HIV-infected) prospectively underwent CCTA at two time points (mean follow-up: 4.0±2.3 years). Agatston-score, number of coronary plaques, segment stenosis score were calculated, and we also segmented the coronary plaques to enumerate total, noncalcified (−100–350HU) and calcified (≥351HU) plaque volumes. Linear mixed models were used to assess the effects of HIV-infection, atherosclerotic cardiovascular disease (ASCVD) risk, years of cocaine use and high-sensitivity C-reactive protein on CCTA markers of CAD. Results In univariate analysis, there was no significant difference in CAD characteristics between HIV-infected and -uninfected, neither at baseline nor at follow-up (p&gt;0.05 for all). Furthermore, there was no significant difference in annual progression rates between the two groups (p&gt;0.05 for all). By multivariate analysis, HIV was not associated with any CAD parameter (p&gt;0.05 for all). However, among HIV-infected individuals, each year of cocaine use significantly increased all CAD parameters (p&lt;0.05 for all), while ASCVD risk score was significantly associated with CAD parameters except for Agatston-score (p&lt;0.05). These associations were only present among HIV-infected individuals. Conclusion(s) Instead of directly worsening CAD, HIV may promote CAD through increased susceptibility to conventional and nonconventional cardiovascular risk factors. Therefore, aggressive management of both conventional and nonconventional cardiovascular risk factors is needed to reduce cardiovascular burden of HIV-infection. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institutes of Health, National Institute on Drug Abuse

Sign in / Sign up

Export Citation Format

Share Document