Unraveling the role of collateral circulation and serum ELAVL1 in carotid atherosclerosis and ischemic stroke: Insights from clinical observations (2024)

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Advances in Clinical and Experimental Medicine

2024, vol. 33, nr 9, September, p. 921–928

doi: 10.17219/acem/172700

Publication type: original article

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

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Song B, Chen X, Pan K, Chen X. Unraveling the role of collateral circulation and serum ELAVL1 in carotid atherosclerosis and ischemic stroke: Insights from clinical observations. Adv Clin Exp Med. 2024;33(9):921–928. doi:10.17219/acem/172700

Bing Song1,C,D, Xiangyue Chen1,A,E,F, Kun Pan2,B,C, Xiaowei Chen1,B

1 Department of Ultrasound, Brain Hospital of Hunan Province, the Second People’s Hospital of Hunan Province, Changsha, China

2 Medical Basic Teaching Experimental Center, Medical College of Hunan University of Chinese Medicine, Changsha, China

Graphical abstract


Unraveling the role of collateral circulation and serum ELAVL1 in carotid atherosclerosis and ischemic stroke: Insights from clinical observations (1)

Abstract

Background. The(embryonic lethal, abnormal vision, drosophila)-like protein 1 (ELAVL1) isanewly discovered protein associated with cerebral ischemic/reperfusion (I/R) injury. However, little isknown ofELAVL1 inischemic stroke patients.

Objectives. Toinvestigate theclinical significance ofcollateral circulation and serum ELAVL1 inpatients with carotid atherosclerosis (CAS) and ischemic stroke.

Materials and methods. Thepresent prospective cohort investigation included 317ischemic stroke patients and 300CAS patients admitted between March 2020 and March 2022. Collateral circulation was measured using digital subtraction angiography (DSA) and graded using theAmerican Society ofInterventional and Therapeutic Neuroradiology/Society ofInterventional Radiology (ASITN/SIR) grading system. Enzyme-linked immunosorbent assays (ELISAs) were used tomeasure serum ELAVL1, C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). Theserum levels oftotal cholesterol (TC), triglyceride (TG), high-density leptin cholesterol (HDL-C), and low-density leptin cholesterol (LDL-C) were also measured.

Results. Theserum levels ofELAVL1, CRP, IL-6, TNF-α, and LDL-C were all markedly higher, while HDL-C was significantly lower inischemic stroke patients compared totheCAS patients. Serum ELAVL1 was markedly higher inASITN/SIR grade 0–1patients compared tograde 2–4patients. Also, ELAVL1 correlated positively with serum CRP, IL-6, TNF-α, TC, and LDL-C, and negatively with HDL-C. Receiver operating characteristic (ROC) curves showed that ELAVL1 and collateral circulation have thepotential tobe used asbiomarkers for thediagnosis ofischemic stroke. Meanwhile, CRP, IL-6, TNF-α, HDL-C, ASITN/SIR grading, and ELAVL1 were independent risk factors for ischemic stroke.

Conclusions. Wefound that serum ELAVL1 was associated with clinical outcomes ofischemic stroke patients, while thecombination ofELAVL1 and collateral circulation could be used asapotential biomarker for ischemic stroke diagnosis.

Key words: ischemic stroke, collateral circulation, carotid atherosclerosis, biomarker, observational study

Background

Stroke isthesecond leading cause ofdisability and mortality worldwide, with over 13million new cases annually.1, 2, 3 Inthepast 50years, theoverall incidence rate ofstroke has shown adownward trend inhigh-income countries and anupward trend inlow- and middle-income countries.4, 5 According tothe2022 global stroke statistics report, theproportion ofpeople over 65years old isproportional totheincidence rate ofstroke, indicating that age isone ofthecritical risk factors for stroke.6, 7 Among stroke patients, over 85% have anischemic stroke, for which carotid atherosclerosis (CAS) isone ofthemost common causes.8, 9 Generally, ischemic stroke iscaused byocclusion ofthemiddle cerebral artery, which leads toneuronal death due toinsufficient blood and oxygen supply tothebrain, resulting inbrain tissue damage.10, 11

Ischemia/reperfusion (I/R) injury isanunavoidable pathological injury instroke patients and amajor cause ofneurological damage.12, 13 Stroke-induced I/R injury can lead topermanent brain tissue damage and may cause cognitive impairment.14, 15 Despite thedevelopment oftreatment strategies, theunderlying molecular mechanisms ofischemic stroke are still unclear.16, 17 Inrecent years, many molecular biomarkers for ischemic stroke have been identified.18, 19 However, new potential biomarkers for ischemic stroke diagnosis and prediction ofprognosis are still needed.

The(embryonic lethal, abnormal vision, drosophila)-like protein 1 (ELAVL1) isanewly discovered protein associated with thedevelopment ofmany diseases, including brain I/R injury, themain pathological alteration inischemic stroke.20, 21, 22 However, no clinical studies have focused onELAVL1 instroke patients. Itiswidely accepted that collateral circulation ischanged and isassociated with theclinical outcomes ofischemic stroke patients.23, 24, 25 Nonetheless, measuring collateral circulation alone might not be accurate enough topredict patients’ clinical outcomes.26

Objectives

Inthepresent study, weaimed toinvestigate theclinical significance ofcollateral circulation and serum ELAVL1 inpatients with CAS and ischemic stroke, focusing ontheir association with patients’ severity and prognosis. Thestudy findings might provide anovel biomarker for CAS and ischemic stroke.

Materials and methods

Patients and study design

Thepresent study was designed asaprospective cohort investigation and included 317ischemic stroke patients admitted toour Department between March 2020 and March 2022. Ischemic stroke diagnosis was based ontheguidelines ofTheChinese Medical Association (2019 update).27, 28 Theinclusion criteria were: 1.all patients were diagnosed with ischemic stroke using imaging methods, including computed tomography angiography (CTA), digital subtraction angiography (DSA) and magnetic resonance imaging (MRI); 2.patients received no anticoagulant therapy within 3months before thestudy. Thefollowing patients were excluded: those receiving anticoagulant therapy within 3months ofstudy commencement, patients with hemorrhagic stroke, and patients with other systematic diseases. Additionally, 300patients with CAS were enrolled ascontrols within thesame study period. Among CAS patients, thefollowing were excluded: patients with severe systematic infections, patients with cancer, and patients with severe cardiovascular, liver orrenal diseases. All patients were consecutively enrolled. Werecruited all cases who met theinclusion criteria during thestudy period. Theethical committee oftheBrain Hospital ofHunan Province (Changsha, China) approved thestudy (Ethics Review Board No. 44; 2021).

Measurement ofcollateral circulation

Thecollateral circulation was measured with DSA and graded using theAmerican Society ofInterventional and Therapeutic Neuroradiology/Society ofInterventional Radiology (ASITN/SIR) grading system, where 0–1means poor compensatory collateral circulation, grade2 ismoderate compensatory circulation, and grade3–4 isgood compensatory circulation.29

Enzyme-linked immunosorbent assay

Blood samples were collected from all patients within 24hofadmission. Enzyme-linked immunosorbent assay (ELISA) was used tomeasure serum ELAVL1 (kit purchased from MyBioSource Inc., San Diego, USA), C-reactive protein (CRP), interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α). Kits for CRP, IL-6, and TNF-α were purchased from Nanjing Jiancheng Bioengineering Institute, Nanjing, China, according tothemanufacturer’s instructions.

Data collection

Demographic data, including age, sex, medical history, and complications, were recorded. Theserum levels oftotal cholesterol (TC), triglyceride (TG), high-density leptin cholesterol (HDL-C), and low-density leptin cholesterol (LDL-C) were measured using anautomatic Hitachi 7600 biochemical analyzer (Hitachi Corporation, Tokyo, Japan).

Statistical analyses

Thedata distribution was analyzed using theKolmogorov–Smirnov method. All measurement data were non-normally distributed and expressed asmedian (range). Comparison between the2groups employed aMann–Whitney Utest, while χ2tests compared rates (without half adjust). Spearman’s analysis was used for correlation analysis. Receiver operating characteristic (ROC) curves were used toevaluate thediagnostic value. Logistic regression was performed toanalyze therisk factor ofischemic stroke. All calculations were made using IBM SPSS v.22.0 (IBM Corporation, Armonk, USA) and GraphPad v.6.0 (GraphPad Software, San Diego, USA), and p<0.05 was defined asstatistically different.

Results

Basic clinical characteristics

Thepresent study included 317ischemic stroke patients and 300CAS patients. Asshown inTable 1, no significant differences were found between the2groups ofpatients for age, sex, body mass index (BMI), orcomplications. However, serum CRP, IL-6, and TNF-α levels were markedly higher inischemic stroke patients compared totheCAS patients (all p<0.05). For lipid metabolism, TC and TG showed no significant difference, while LDL-C was remarkably higher and HDL-C was significantly lower inischemic stroke patients (p<0.05). For ASITN/SIR grading, thefrequency ofgrade0–1 was significantly higher inischemic stroke patients compared totheCAS patients (p<0.05).

Serum ELAVL1 was associated withcollateral circulation

Tofurther investigate therole ofELAVL1 inCAS and ischemic stroke patients, thelevels ofELAVL1 indifferent patients were determined. Serum ELAVL1 was significantly upregulated inischemic stroke patients compared totheCAS patients (p<0.05, Figure 1A). Furthermore, serum ELAVL1 was markedly higher inASITN/SIR grade 0–1patients than ingrade 2–4patients (p<0.05, Figure 1B). These results indicated that serum ELAVL1 might be associated with collateral circulation inCAS and ischemic stroke patients.

Serum ELAVL1 was associated withinflammatory cytokines andlipidmetabolism

Weconducted additional correlation analysis for serum ELAVL1, inflammatory cytokines, and lipid metabolism. Asshown inTable 2, serum ELAVL1 was positively correlated with serum CRP, IL-6, TNF-α, TC, and LDL-C, and negatively correlated with HDL-C (all p<0.05), suggesting that serum ELAVL1 was associated with theclinical outcomes ofCAS inischemic stroke patients.

Diagnostic value ofELAVL1 and collateral circulation for ischemic stroke

TheROC curves were used todetermine thediagnostic value ofELAVL1 and collateral circulation for ischemic stroke. TheELAVL1 showed good diagnostic value for ischemic stroke, with anarea under thecurve (AUC)=0.904, sensitivity=79.18%, specificity=78.67%, and acutoff value>10.56ng/mL (Figure 2A). Collateral circulation (ASITN/SIR grading) also demonstrated diagnostic value for ischemic stroke, with anAUC=0.625, sensitivity=61.88%, specificity=54.20%, and acutoff value<2.5 (Figure 2B).

When practicing thediagnostic mode inthepatients using thecutoff value, both ELAVL1 and ASITN/SIR grading could be used asdiabetic markers. Thecombination ofELAVL1 and ASITN/SIR grading showed better sensitivity and accuracy (Table 3). All ofthese results imply that ELAVL1 and collateral circulation have thepotential tobe used asbiomarkers for thediagnosis ofischemic stroke. Figure 3 shows atypical DSA image ofthecollateral circulation.

Risk factors for ischemic stroke bylogisticregression

Finally, weused univariate and multivariate logistic regression toanalyze therisk factors for ischemic stroke. Inunivariate logistic regression, CRP, IL-6, TNF-α, LDL-C, HDL-C, ASITN/SIR grading, and ELAVL1 were risk factors for ischemic stroke. While inmultivariate logistic regression, CRP, IL-6, TNF-α, HDL-C, ASITN/SIR grading, and ELAVL1 were independent risk factors for ischemic stroke (Table 4).

Discussion

Stroke istheprimary cause ofdeath inChina. According todata from China’s National Stroke Epidemiology Survey, theage-standardized incidence rate ofstroke inadults isapprox. 1115cases per 100,000 individuals, with amortality rate of115per 100,000.30 Over thepast decade, while theincidence rates have been decreasing inhigh-income countries, China has seen agradual increase instroke incidence, though themortality rate has remained relatively stable.31, 32 Ischemic strokes primarily result from occlusion ofthecerebral arteries, leading toinsufficient blood and oxygen supply tothebrain, causing neuronal death and subsequent brain tissue damage.

Currently, ischemic stroke treatment mainly involves thrombolysis, anticoagulation therapy, and surgical interventions.33 However, theoccurrence ofI/R injury after treatment often proves difficult toavoid and constitutes amajor contributor toneuronal damage. Nonetheless, there are currently no specific drugs ortherapies available toeffectively address I/R injury and theresulting cognitive impairments following stroke. Thus, timely diagnosis ofischemic stroke isofgreat significance for patients’ treatment and prognosis. Inthepresent study, wedemonstrated that serum ELAVL1 was elevated inischemic stroke patients and correlated with collateral circulation and clinical outcomes. Assuch, combining collateral circulation and ELAVL1 could be used asapotential biomarker for ischemic stroke diagnosis.

TheELAVL1 isanewly discovered protein associated with thedevelopment ofmany diseases, such ascardiovascular disease (CVD) and cerebral I/R injury. Inmyocardial I/R injury, ELAVL1 was significantly elevated, and knockdown ofELAVL1 could inhibit ferroptosis and improve I/R injury.34 Du etal. demonstrated that ELAVL1 was upregulated incerebral I/R injury and facilitated neurobehavioral impairments and brain infractions after I/R treatment inanimal models.22 Inanearly study, ELAVL1 expression was increased inhuman hearts and ventricular cardiomyocytes under hyperglycemic conditions and was accompanied byincreased inflammation and pyroptosis.35 However, up until now, no study has reported onELAVL1 instroke and CAS patients.

Inthepresent research, wedemonstrated ELAVL1 upregulation inischemic stroke patients for thefirst time, which was associated with inflammation and lipid metabolism, and correlated with collateral circulation. Furthermore, higher levels ofELAVL1 were associated with worse clinical outcomes, consistent with invitro and animal studies using ischemia models. Besides myocardial injury, ELAVL1 also facilitates cellular injury inother diseases. Arecent study reported that ELAVL1 knockdown led tothesuppression ofpyroptosis byinhibiting NLRP3 (NLR family pyrin domain containing 3) intheHK-2 renal tubular cell model ofdiabetic nephropathy.36 Inkidney I/R injury, ELAVL1 promoted ferritinophagy inHK-2 cells and thus aggravated ferroptosis and oxidative stress.37 Similar results are also shown inParkinson’s disease.

Researchers found that elevated ELAVL1 and NLRP3 induced pyroptosis, while downregulation ofELAVL1 inhibited pyroptosis, pyroptosis-induced inflammation and oxidative stress.38 These studies imply acorrelation between ELAVL1 and inflammation/oxidative stress, which was also seen inour work, where wedemonstrated ELAVL1 was positively correlated with serum CRP, IL-6 and TNF-α. Thus, wespeculate that theupregulation ofELAVL1 inischemic stroke patients isalso related toincreased inflammatory responses and oxidative stress. However, wedid not measure oxidative stress inthis study.

Collateral circulation has been widely investigated instroke patients. Itwas reported that patients with good DSA collaterals had markedly smaller hypoperfusion volumes and perfusion mismatch volumes, which was also associated with thehypoperfusion intensity ratio.39 Inanother study, Sui etal. demonstrated that ASITN/SIR grading was associated with theNational Institutes for Health Stroke Scale (NHISS) and prognosis ofwake-up stroke patients.40 Inameta-analysis, theauthors demonstrated that collateral circulation status and final infarct volume (FIV) are independent outcome predictors for ischemic stroke patients.41 Amore recent study investigated theshort-term prognosis ofwake-up stroke patients and found that patients with ASITN/SIR grade 2–3had lower NIHSS and modified Rankin scores (mRS) and higher Barthel index (BI) scores after treatment, indicating collateral circulation isassociated with theprognosis ofwake-up stroke patients.40 However, arecent study demonstrated that inter- and intraobserver agreement ofcollateral circulation grading using theASITN/SIR score was poor,26 suggesting that ASITN/SIR grading alone might not be accurate enough for predicting clinical outcomes ofischemic stroke patients.

Inaddition toischemic stroke, ASITN/SIR grading isalso used tomeasure collateral circulation inintracranial arterial stenosis and subarachnoid hemorrhage.42, 43 Inour study, wealso found that thefrequency of0–1ASITN/SIR grading was markedly higher inischemic stroke patients. Besides, weobserved that ELAVL1 was negatively associated with ASITN/SIR grades, and when combined, they have thepotential for ischemic stroke diagnosis. These findings may provide apotential and novel method for theprediction/diagnosis ofischemic stroke.

Limitations

Thestudy had some limitations. Thesample size was small, and thepatients were all from asingle center. Furthermore, themolecular mechanisms ofELAVL1 inischemic stroke need tobe illustrated infuture studies. Tofurther understand therole ofELAVL1 inischemic stroke, wewill conduct studies using both myocardial I/R injury animal models and cellular models. Also, expanding thesample size inclinical investigations isneeded inthefuture.

Conclusions

Serum ELAVL1 was associated with clinical outcomes ofischemic stroke patients. Thecombination ofELAVL1 and collateral circulation could be used asapotential strategy for thediagnosis ofischemic stroke. All ofthese results might provide anovel method for thediagnosis ofischemic stroke patients. Since timely treatment iscritical, especially inacute ischemic stroke, wethink that early diagnosis isofgreat significance. Thus, novel serum markers may help physicians gather more information onthepatients’ condition and better understand therisk for patients susceptible tostroke. However, more clinical and basic studies are still needed toprovide deeper insights into therole ofELAVL1 inischemic stroke.

Data availability

All original data can be obtained from thecorresponding author onproper request.

Consent for publication

Not applicable.

Tables


Table 1. Basic characteristics ofall patients

Variables

Ischemic stroke (n=317)

CAS (n=300)

p-value

Age [years]

52 (35–70)

51 (35–70)

0.891

Sex (male : female, %)

179 (56.47) : 138 (43.53)

165 (55.00) : 135 (45.00)

0.834

BMI [kg/m2]

25.12 (18.01–31.99)

24.57 (18.03–31.74)

0.714

Complications, n(%)

diabetes

75 (23.66)

70 (23.33)

0.735

hypertension

69 (21.77)

57 (19.00)

current smoker

141 (44.48)

124 (41.33)

CRP [mg/L]

27.24 (5.32–49.73)

12.67 (3.02–24.95)

<0.001

IL-6 [pg/mL]

32.29 (5.05–59.90)

16.95 (5.04–29.98)

<0.001

TNF-α [pg/mL]

22.98 (5.01–39.85)

12.24 (5.02–19.85)

<0.001

TC [mmol/L]

4.36 (3.25–5.37)

4.22(3.26–5.38)

0.189

TG [mmol/L]

1.49 (0.93–2.02)

1.44 (0.94–2.01)

0.659

LDL-C [mmol/L]

3.15 (2.21–4.00)

2.88 (2.17–3.79)

<0.001

HDL-C [mmol/L]

1.10 (0.95–1.23)

1.12 (0.97–1.25)

0.002

ASITN/SIR grading, n(%)

0–1

194 (61.20)

85 (28.33)

<0.001

2–4

123 (38.80)

215 (71.67)

Thep-values were calculated between CAS and ischemic stroke patients using Student’s t-test ofMann–Whitney Utest for normally ornon-normally distributed data, respectively. χ2 test was used for comparing rates. CAS –carotid atherosclerosis; BMI –body mass index; CRP –C-reactive protein;
IL-6 –interleukin 6; TNF-α –tumor necrosis factor alpha; TC –total cholesterol; TG –triglyceride; LDL-C –low-density-lipoprotein cholesterol; HDL-C –high-density-lipoprotein cholesterol;
ASITN/SIR –American Society ofInterventional and Therapeutic Neuroradiology/Society ofInterventional Radiology.

Table 2. Spearman’s correlation among serum (embryonic lethal, abnormal vision, drosophila)-like protein 1 (ELAVL1), inflammatory cytokines and lipid metabolism inall patients

Variables

Spearman’s correlation

p-value

CRP

0.354

<0.001

IL-6

0.334

<0.001

TNF-α

0.335

<0.001

TC

0.098

0.015

TG

−0.019

0.632

LDL-C

0.146

<0.001

HDL-C

−0.076

0.049

BMI –body mass index; CRP –C-reactive protein; IL-6 –interleukin 6;
TNF-α –tumor necrosis factor alpha; TC –total cholesterol; TG–triglyceride; LDL-C –low-density-lipoprotein cholesterol;
HDL-C –high-density-lipoprotein cholesterol.

Table 3. Diagnostic value of(embryonic lethal, abnormal vision, drosophila)-like protein 1 (ELAVL1) and collateral circulation for ischemic stroke

Methods

True positive

False positive

True negative

False negative

Sensitivity

Specificity

Accuracy

ELAVL1

251

64

236

66

79.18%

78.67%

78.93%

ASITN/SIR grading

232

158

142

85

73.19%

47.33%

60.62%

ELAVL1 + ASITN/SIR grading

300

188

112

17

94.64%

37.33%

66.77%

* Sensitivity=true positive/(true positive + false negative)×100%; specificity=true negative/(true negative + false positive)×100%; accuracy=(true positive + true negative)/(true positive + false negative + false positive + true negative)×100%; ASITN/SIR –American Society ofInterventional and Therapeutic Neuroradiology/Society ofInterventional Radiology.

Table 4. Logistic regression for risk factors ofunstable plaque

Variables

Univariate

Multivariate

OR

95% CI

p-value

OR

95% CI

p-value

Age

0.999

0.984–1.014

0.893

0.985

0.944–1.028

0.488

Sex

1.061

0.772–1.458

0.714

1.388

0.546–3.528

0.490

BMI

0.992

0.955–1.032

0.699

1.041

0.931–1.164

0.479

Diabetes

0.982

0.677–1.425

0.924

0.678

0.243–1.890

0.458

Hypertension

0.843

0.569–1.249

0.395

1.058

0.326–3.435

0.925

Current smoker

0.879

0.639–1.210

0.430

0.562

0.217–1.455

0.235

CRP

0.862

0.840–0.883

<0.001

0.818

0.766–0.873

<0.001

IL-6

0.896

0.879–0.914

<0.001

0.868

0.823–0.916

<0.001

TNF-α

0.843

0.818–0.868

<0.001

0.804

0.746–0.867

<0.001

TC

0.840

0.649–1.089

0.189

1.144

0.560–2.336

0.712

TG

0.896

0.547–1.466

0.661

0.910

0.234–3.536

0.892

LDL-C

0.445

0.322–0.616

<0.001

0.613

0.245–1.536

0.296

HDL-C

26.709

3.701–192.777

0.001

8452.881

24.213–2.95×106

0.002

ASITN/SIR grading

1.520

1.348–1.714

<0.001

0.433

0.331–0.566

<0.001

ELAVL1

0.561

0.512–0.615

<0.001

1.560

1.122–2.170

0.008

95% CI –95% confidence interval; OR –odds ratio; BMI –body mass index; CRP –C-reactive protein; IL-6 –interleukin 6; TNF-α –tumor necrosis factor alpha; TC –total cholesterol; TG –triglyceride; LDL-C –low-density-lipoprotein cholesterol; HDL-C –high-density-lipoprotein cholesterol; ELAVL1 –(embryonic lethal, abnormal vision, drosophila)-like protein 1; ASITN/SIR –American Society ofInterventional and Therapeutic Neuroradiology/Society ofInterventional Radiology.

Figures


Fig. 1. A.Serum ELAV (embryonic lethal, abnormal vision, drosophila)-like protein 1 (ELAVL1) was evaluated inischemic stroke patients using anenzyme-linked immunosorbent assay (ELISA) and compared tocarotid atherosclerosis (CAS) patients; B.Serum ELAVL1 was evaluated using ELISA inpatients with different American Society ofInterventional and Therapeutic Neuroradiology/Society ofInterventional Radiology (ASITN/SIR) grades. Lines indicate themedian (range)

Unraveling the role of collateral circulation and serum ELAVL1 in carotid atherosclerosis and ischemic stroke: Insights from clinical observations (2)

Fig. 2. A.Receiver operating characteristic (ROC) curve ofELAV (embryonic lethal, abnormal vision, drosophila)-like protein 1 (ELAVL1) for thediagnosis ofischemic stroke; B. ROC curve ofAmerican Society ofInterventional and Therapeutic Neuroradiology/Society ofInterventional Radiology (ASITN/SIR) grading for diagnosis ofischemic stroke

Unraveling the role of collateral circulation and serum ELAVL1 in carotid atherosclerosis and ischemic stroke: Insights from clinical observations (3)

Fig. 3. Atypical digital subtraction angiography (DSA) image ofcollateral circulation from a52-year-old male patient

Unraveling the role of collateral circulation and serum ELAVL1 in carotid atherosclerosis and ischemic stroke: Insights from clinical observations (4)

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Unraveling the role of collateral circulation and serum ELAVL1 in carotid atherosclerosis and ischemic stroke: Insights from clinical observations (2024)

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