Transcriptomic signatures for human male infertility.

Introduction: Male infertility is a common, complex disorder. A better understanding of pathogenesis and etiology is needed for timely diagnosis and treatment. The aim of this study, therefore, was to identify genes involved in the pathogenesis of idiopathic male infertility based on data from transcriptomic level supported with data from genomic level. Materials and methods: First, we performed whole gene expression analysis in 20 testis biopsy samples of patients with severely impaired (10) and normal spermatogenesis (10). Further, we have performed systematic review of comparable male infertility studies and overlapped the most significantly expressed genes identified in our study with the most differentially expressed genes from selected studies. Gene Ontology analysis and KEGG functional enrichment have been performed with Enrichr analysis tool. Additionally, we have overlapped these genes with the genes where rare variants have been identified previously. Results: In 10 patients with severely impaired spermatogenesis and 10 controls, we identified more than 1,800 differentially expressed genes (p < 0.001). With the systematic review of three previously performed microarray studies that have met inclusion criteria we identified 257 overlapped differentialy expressed genes (144 downregulated and 113 upregulated). Intersection of genes from transcriptomic studies with genes with identified rare variants revealed a total of 7 genes linked with male infertility phenotype (CYP11A1, CYP17A1, RSPH3, TSGA10, AKAP4, CCIN, NDNF). Conclusion: Our comprehensive study highlighted the role of four genes in pathogenesis of male infertility and provided supporting evidence for three promising candidate genes which dysfunction may result in a male infertility disorder.

The Role of ACE, ACE2, and AGTR2 Polymorphisms in COVID-19 Severity and the Presence of COVID-19-Related Retinopathy.

The proposed SARS-CoV-2-induced dysregulation of the renin-angiotensin-aldosterone (RAAS) system results in endothelial dysfunction and microvascular thrombosis. The retinal plexuses contain terminal vessels without anastomotic connections, making the retina especially susceptible to ischemia. This study aimed to determine the role of selected polymorphisms of genes in the RAAS pathway in COVID-19 severity and their association with the presence of COVID-19 retinopathy. 69 hospitalized patients in the acute phase of COVID-19 without known systemic comorbidities and 96 healthy controls were enrolled in this prospective cross-sectional study. The retina was assessed with fundus photography using a Topcon DRI OCT Triton (Topcon Corp., Tokyo, Japan) in the COVID-19 unit. Genotyping of selected polymorphisms in the genes for ACE (rs4646994), ACE2 (rs2285666), and AGTR2 (rs1403543) was performed. The COVID-19 group was divided into mild (n = 12) and severe (n = 57), and then further divided according to the presence of COVID-19 retinopathy (Yes, n = 50; No, n = 19). The presence of the AGTR2 rs1403543-AA genotype was associated with a 3.8-fold increased risk of COVID-19 retinopathy (p = 0.05). The genotype frequencies of selected gene polymorphisms were not significantly associated with either the presence of COVID-19 or its severity. This is the first study demonstrating a borderline association of the AGTR2 rs1403543-AA genotype with COVID-19 retinopathy in males; hence, the AGTR2 rs 1403543 A allele might represent a genetic risk factor for COVID-19 retinopathy in males.

Association between the rs2279238 of the Liver X receptor alpha gene polymorphism and advanced carotid atherosclerosis in the Slovenian cohort.

BACKGROUND: Liver X receptor alpha (LXRA) plays important role in cholesterol and lipid homeostasis and lipid metabolism; moreover, it has been investigated as a candidate gene in a number of conditions, including onset and progression of atherosclerosis. We hypothesized that the LXRA gene rs2279238 polymorphism may be associated with the onset and progression of carotid atherosclerosis in the Slovenian cohort. METHODS: 783 unrelated Slovenian patients were included in this cross-sectional case-control study: 308 patients in the group of cases with severe internal carotid artery (ICA) stenosis (>75 %) and 475 patients with hemodynamically insignificant ICA stenosis (<50 %) in the control group. Medical records were used to acquire patient laboratory and clinical data. The TaqMan SNP Genotyping assay was used to genotype the rs2279238 polymorphism. RESULTS: Between the case and control groups, we identified a statistically significant variation in genotype distribution (p = 0.04), but not in allele frequency (p = 0.13) of the LXRA gene polymorphism rs2279238. The results, also show that there is a statistically significant association (p = 0.04) between the two genetic models (codominant and recessive) of the LXRA gene rs2279238 polymorphism and carotid atherosclerosis. CONCLUSION: In the Slovenian cohort, we found a significant association between the TT genotype of rs2279238 and advanced carotid artery disease, suggesting that this polymorphism might be a genetic risk factor for ICA atherosclerosis.

Association of Myocardial Infarction with CDKN2B Antisense RNA 1 (CDKN2B-AS1) rs1333049 Polymorphism in Slovenian Subjects with Type 2 Diabetes Mellitus.

BACKGROUND: We examined the role of rs1333049 polymorphism of the CDKN2B Antisense RNA 1 (CDKN2B-AS1) on the prevalence of myocardial infarction (MI) in Slovenian subjects with type 2 diabetes mellitus (T2DM). METHODS: A total of 1071 subjects with T2DM were enrolled in this retrospective cross-sectional case-control study. Of the subjects, 334 had a history of recent MI, and 737 subjects in the control group had no clinical signs of coronary artery disease (CAD). With logistic regression, we performed a genetic analysis of rs1333049 polymorphism in all subjects. RESULTS: The C allele of rs1333049 polymorphism was statistically more frequent in MI subjects (p = 0.05). Subjects with CC genotype had a higher prevalence of MI than the control group in the co-dominant (AOR 1.50, CI 1.02-2.21, p = 0.04) and recessive (AOR 1.38, CI 1.09-1.89, p = 0.04) genetic model. CONCLUSIONS: According to our study, the C allele and CC genotype of rs1333049 polymorphism of CDKN2B-AS1 are possible markers of MI in T2DM subjects in the Slovenian population.

HDAC9 rs11984041 polymorphism is associated with diabetic retinopathy in Slovenian patients with type 2 diabetes mellitus.

AIM: Histone deacetylase 9 (HDAC9) is an important regulator of transcription that has also been investigated as a candidate gene in some pathologies. Our aim was to investigate the association between rs2107595 and rs11984041 HDAC9 gene polymorphisms and diabetic retinopathy (DR) in Slovenian patients with type 2 diabetes mellitus (T2DM). We also investigated HDAC9 expression in the fibrovascular membranes (FVMs) of patients with proliferative DR (PDR). METHODS: Our study involved 1290 unrelated Slovenian patients with T2DM: 542 of them with DR as the study group, and 748 without DR as the control group. The investigated polymorphisms were genotyped using KASPar genotyping assay. The expression of HDAC9 was examined by immunohistochemistry in human FVM from 25 patients with PDR. RESULTS: The T allele and TT genotype frequencies of the rs11984041 polymorphism were significantly higher in the study group compared to the controls. The logistic regression analysis showed that the carriers of the TT genotype of this polymorphism have a 3.76-fold increase (95% CI 1.04-11.67) in the risk of developing DR. The T allele of rs11984041 was associated with increased HDAC9 expression in FVMs, obtained from T2DM patients with PDR. Patients with the T allele of rs11984041 compared to the homozygotes for the wild type C allele exhibited higher density of HDAC9-positive cells (35 ± 10/mm2 vs. 12 ± 6/mm2, respectively). CONCLUSIONS: We observed a notable association between the TT genotype of rs11984041 and DR, indicating its possible role as a genetic risk factor for the development of this diabetic complication.

The C allele of the reactive oxygen species modulator 1 (ROMO1) polymorphism rs6060566 is a biomarker predicting coronary artery stenosis in Slovenian subjects with type 2 diabetes mellitus.

BACKGROUND: We aimed to examine the role of the rs6060566 polymorphism of the reactive oxygen species modulator 1 (ROMO1) gene in the development of myocardial infarction (MI) in Caucasians with type 2 diabetes (T2DM). METHODS: A total of 1072 subjects with T2DM were enrolled in this cross-sectional case-control study: 335 subjects with MI and 737 subjects without clinical signs of coronary artery disease (CAD). The genetic analysis of the rs6060566 polymorphism was performed in all subjects. To assess the degree of coronary artery obstruction, a subpopulation of 128 subjects with T2DM underwent coronary computed tomography angiography. Next, endarterectomy samples were obtained during myocardial revascularization from diffusely diseased coronary arteries in 40 cases, which were analysed for ROMO1 expression according to their genotype. RESULTS: There were no statistically significant associations between different genotypes or alleles of the rs6060566 polymorphism and MI in subjects with T2DM. The carriers of the C allele of the ROMO1 rs6060566 had a threefold increased likelihood of having 50-75% coronary artery stenosis (Adjusted OR = 3.27, 95% CI 1.16-9.20). Subjects with two affected coronary arteries had a 3.72 fold higher prevalence of MI (OR = 3.72, 95% CI 1.27-10.84). With CAD in LMCA or LAD, MI prevalence was about 3.5-fold higher (p = 0.07 for LMCA and p = 0.01 for LAD). Furthermore, the carriers of the rs6060566 C allele showed higher number of positive cells for ROMO1 expression in endarterectomy samples of coronary arteries. CONCLUSIONS: According to our study, the rs6060566 polymorphism of the ROMO1 gene is not a risk factor for MI in Caucasians with T2DM. However, we found that subjects carrying the C allele were at a 3.27-fold increased risk of developing severe CAD compared with those who had non-obstructive CAD. Moreover, C allele carriers showed a statistically higher number of cells positive for ROMO1 compared with T allele carriers in coronary endarterectomy samples.

Correlations between vitreous cytokine levels and inflammatory cells in fibrovascular membranes of patients with proliferative diabetic retinopathy.

Purpose: The purpose of this study was to investigate the levels of cytokines in the vitreous, and their correlation with the density of inflammatory cells in fibrovascular membranes (FVMs) in patients with proliferative diabetic retinopathy (PDR) to evaluate intraocular inflammatory conditions with regard to disease activity. Methods: Thirty-three patients (33 eyes) with PDR requiring vitreoretinal surgery because of FVMs and tractional detachment were enrolled in the study, and compared with 20 patients (20 eyes) with macular hole (MH; control group). All patients underwent complete ophthalmological examinations before surgery. The activity of the disease was noted in patients with PDR. Samples of vitreous and blood were taken, and cytokine (MCP-1, IL-8, IL-6, VEGF, IL-1ß, TNF-α, MIP-1α, MIP-1ß, IL-10, and IL-12) levels were measured using cytometric bead array (CBA). Samples of FVMs were analyzed with immunohistochemical methods for the presence of inflammatory cells (CD45+, CD14+, CD3+, CD4+, CD8+, and CD19+ cells), and the numerical areal density was calculated (NA). Spearman's correlation was used to assess the association between variables. The Mann-Whitney test was used to assess the differences between independent groups. The Wilcoxon signed-rank test was used for assessing differences between two related groups. A p value of less than 0.05 was considered statistically significant. Results: Patients with active PDR had statistically significantly higher levels of MCP-1 (p = 0.003), VEGF (p = 0.009), and IL-8 (p = 0.02) in the vitreous in comparison with those with inactive PDR. CD45+, CD14+, CD3+, CD4+, CD8+, and CD19+ cells were identified in FVMs for patients with PDR. Statistically significantly higher numerical areal density of T lymphocytes (CD3+, CD4+, and CD8+) was demonstrated in patients with active PDR in comparison with patients with inactive PDR. Moderate to strong correlations were found between either MCP-1 or IL-8 in the vitreous, and the numerical areal density of cells (CD45+, CD3+, CD4+, and CD8+) in the FVMs, and weaker between either MCP-1 or IL-8 in the vitreous and the numerical areal density of CD14+ cells in the FVMs. Conclusions: The correlation of cytokine (MCP-1 and IL-8) vitreous levels with the density of inflammatory cells in FVMs, and differences in cytokine levels in the vitreous between patients with active and inactive PDR, and between the vitreous and serum in PDR indicate the importance of local intraocular inflammation in patients with PDR.

Association between rs2107595 HDAC9 gene polymorphism and advanced carotid atherosclerosis in the Slovenian cohort.

BACKGROUND: Histone deacetylase 9 (HDAC9) plays an important role in transcriptional regulation, cell cycle progression and developmental events; moreover, it has been investigated as a candidate gene in a number of conditions, including the onset and progression of atherosclerosis. We hypothesized that the rs2107595 HDAC9 gene polymorphism may be associated with advanced carotid artery disease in a Slovenian cohort. We also investigated the effect of this polymorphism on HDAC9 receptor expression in the internal carotid artery (ICA) specimens obtained by endarterectomy. METHODS: This case-control study enrolled 619 unrelated Slovenian patients: 311 patients with ICA stenosis > 75% as the study group and 308 patients with ICA stenosis < 50% as the control group. Patient laboratory and clinical data were obtained from the medical records. The rs2107595 polymorphisms were genotyped using TaqMan SNP Genotyping assay. HDAC9 expression was assessed by immunohistochemistry in 30 ICA specimens from patients with ICA atherosclerosis > 75%, and the numerical areal density of HDAC9 positive cells was calculated. RESULTS: The occurrence of advanced ICA atherosclerosis in the Slovenian cohort was 3.81 times higher in the codominant genetic model (OR = 3.81, 95%CI = 1.06-13.77, p = 0.04), and 3.10 times higher in the recessive genetic model (OR = 3.10, 95%CI = 1.16-8.27, p = 0.02). In addition, the A allele of rs2107595 was associated with increased HDAC9 expression in the ICA specimens obtained by endarterectomy. CONCLUSIONS: We observed a significant association between the AA genotype of rs2107595 with the advanced carotid artery disease in our Slovenian cohort, indicating that this polymorphism may be a genetic risk factor for ICA atherosclerosis.

Circadian clock genes and myocardial infarction in patients with type 2 diabetes mellitus.

Disruption of circadian clock may trigger the onset of diabetes mellitus and myocardial infarction. Type 2 diabetes mellitus (T2DM) is well-known risk factors for cardiovascular diseases and myocardial infarction. We performed a case-control study, where we explored the possible association between single nucleotide polymorphisms in three circadian rhythm genes (ARNTL, CLOCK, and PER2) and myocardial infarction in 657 patients with T2DM. The study group consisted of 231 patients with myocardial infarction and T2DM and a control group of 426 T2DM patients. We hypothesized that variations in the circadian rhythm genes in patients with T2DM could be an additional risk factor for myocardial infarction. The statistically significant difference was found in allelic (p = 1.1 × 10-5) and genotype distribution (p = 1.42 × 10-4) between two groups of the rs12363415 at the ARNTL gene locus. We provide evidence that genetic variability in the ARNTL gene might be associated with myocardial infarction in patients with T2DM.

Screening for Rare Genetic Variants Associated with Atherosclerosis: Opportunity for Personalized Medicine.

Atherosclerosis and its clinical manifestations is a leading cause of disease burden worldwide. Currently, most of the individuals carrying a strong predisposition to complications of atherosclerosis because of monogenic dyslipidaemias remain undiagnosed and consequently are not given an opportunity for prevention. Therefore, one of the main public health challenges remains the identification of individuals with significantly increased risk for atherosclerosis due to monogenic predisposition. Next-Generation Sequencing (NGS) has revolutionized genetic testing in symptomatic patients. Although new genomic technologies are still developing, and evidence on the use of this methodology for screening purposes is still lacking, genome testing might provide a powerful tool for the identification of individuals at risk. This may pave the way for the implementation of personalized medicine in the field of atherosclerosis prevention. In this review, we discuss the potential of genetic screening for atherosclerosis prevention and present the potential target of 17 genes responsible for monogenic dyslipidaemias associated with atherosclerosis.

Genetic Variations and Subclinical Markers of Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus.

Atherosclerosis and its cardiovascular complications are the main cause of death in diabetic patients. Patients with diabetes mellitus have a greater than 10-fold risk of cardiovascular disease in their lifetime. The carotid Intima-Media Thickness (cIMT), a surrogate marker for the presence and progression of atherosclerosis, predicts future cardiovascular events in asymptomatic subjects with Type 2 Diabetes Mellitus (T2DM). This review focuses on genetic variants that contribute to the pathobiology of subclinical atherosclerosis in the setting of T2DM. Specifically, we devoted our attention to wellstudied genes selected for their relevance for atherosclerosis. These include: The Renin-Angiotensin- Aldosterone System (RAAS), Apolipoprotein E (ApoE), Methylenetetrahydrofolate Reductase (MTHFR) and pro-inflammatory genes. The ever-growing availability of advanced genotyping technologies has made Genome-Wide Association Studies (GWAS) possible. Although several bioinformatics tools have been developed to manage and interpret the huge amounts of data produced, there has been limited success in the many attempts to uncover the biological meaning of the novel susceptibility loci for atherosclerosis.

Markers of Atherosclerosis: Part 1 - Serological Markers.

Atherosclerosis is a major contributor to morbidity and mortality worldwide. With therapeutic consequences in mind, several risk scores are being used to differentiate individuals with low, intermediate or high cardiovascular (CV) event risk. The most appropriate management of intermediate risk individuals is still not known, therefore, novel biomarkers are being sought to help re-stratify them as low or high risk. This narrative review is presented in two parts. Here, in Part 1, we summarise current knowledge on serum (serological) biomarkers of atherosclerosis. Among novel biomarkers, high sensitivity C-reactive protein (hsCRP) has emerged as the most promising in chronic situations, others need further clinical studies. However, it seems that a combination of serum biomarkers offers more to risk stratification than either biomarker alone. In Part 2, we address genetic and imaging markers of atherosclerosis, as well as other developments relevant to risk prediction.

Markers of Atherosclerosis: Part 2 - Genetic and Imaging Markers.

This is Part 2 of a two-part review summarising current knowledge on biomarkers of atherosclerosis. Part 1 addressed serological biomarkers. Here, in part 2 we address genetic and imaging markers, and other developments in predicting risk. Further improvements in risk stratification are expected with the addition of genetic risk scores. In addition to single nucleotide polymorphisms (SNPs), recent advances in epigenetics offer DNA methylation profiles, histone chemical modifications, and micro-RNAs as other promising indicators of atherosclerosis. Imaging biomarkers are better studied and already have a higher degree of clinical applicability in cardiovascular (CV) event prediction and detection of preclinical atherosclerosis. With new methodologies, such as proteomics and metabolomics, discoveries of new clinically applicable biomarkers are expected.

Vascular endothelial growth factor (VEGF)-related polymorphisms rs10738760 and rs6921438 are not risk factors for proliferative diabetic retinopathy (PDR) in patients with type 2 diabetes mellitus (T2DM).

Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis and has been investigated as a candidate gene in a number of conditions, including diabetes and its microvascular complications (e.g., retinopathy and nephropathy). Several VEGF-related polymorphisms have been shown to contribute to nearly half of the variability in circulating VEGF levels in healthy individuals. Our aim was to assess the association between VEGF-related rs10738760 and rs6921438 polymorphisms and proliferative diabetic retinopathy (PDR) in Slovenian patients with type 2 diabetes mellitus (T2DM). We also investigated the effect of these polymorphisms on VEGF receptor 2 (VEGFR-2) expression in fibrovascular membranes (FVMs) from patients with PDR. This case-control study enrolled 505 unrelated patients with T2DM: 143 diabetic patients with PDR as a study group, and 362 patients with T2DM of >10 years duration and with no clinical signs of PDR as a control group. Patient clinical and laboratory data were obtained from their medical records. rs10738760 and rs6921438 polymorphisms were genotyped using TaqMan SNP Genotyping assay. VEGFR-2 expression was assessed by immunohistochemistry in 20 FVMs from patients with PDR, and numerical areal density of VEGFR-2-positive cells was calculated. The occurrence of PDR was 1.7 times higher in diabetic patients carrying GA genotype of rs6921438 compared to patients with GG genotype, with a borderline statistical significance (OR = 1.7, 95% CI = 1.00 - 2.86, p = 0.05). In addition, A allele of rs6921438 was associated with increased VEGFR-2 expression in FVMs from PDR patients. However, we observed no association between AA genotype of rs6921438 nor between rs10738760 variants and PDR, indicating that the two polymorphisms are not genetic risk factors for PDR.

Interleukin-4 (IL4) -590C/T (rs2243250) gene polymorphism is not associated with diabetic nephropathy (DN) in Caucasians with type 2 diabetes mellitus (T2DM).

Diabetic nephropathy (DN) is a microvascular complication that affects up to 40% of diabetic patients and can lead to end-stage kidney disease. Inflammatory cytokines such as interleukin 1 (IL-1), IL-6, IL-18 and tumor necrosis factor-α (TNFα) have been linked to the development and progression of DN. The aim of our study was to examine the relationship between interleukin-4 (IL4) -590C/T (rs2243250) gene polymorphism and DN in patients with type 2 diabetes mellitus (T2DM). This study is a continuation of our previous research on the association between angiotensinogen (AGT) gene polymorphisms and DN in patients with T2DM. We included 651 unrelated Slovenian (Caucasian) patients who had had T2DM for at least 10 years. The participants were classified into a group of T2DM patients with DN (276 cases) and a group without DN (375 controls). IL4 rs2243250 polymorphism was analyzed using a TaqMan SNP genotyping assay and StepOne Real-Time PCR System. The frequencies of rs2243250 TT, CT and CC (wild type) genotypes were 3.2%, 29.4% and 67.4%, respectively in patients with DN, and 2.7%, 34.4% and 62.9%, respectively in controls. Our logistic regression analysis adjusted for gender, age, diabetes duration, and glycated hemoglobin showed no association between rs2243250 and the risk for DN (OR 1.06; CI 0.37-3.05; p = 0.9). IL4 rs2243250 is not associated with DN in our subset of Slovenian patients with T2DM.

Melatonin and breast cancer: Evidences from preclinical and human studies.

The breast cancer affects women with high mortality and morbidity worldwide. The risk is highest in the most developed world but also is markedly rising in the developing countries. It is well documented that melatonin has a significant anti-tumor activities demonstrated on various cancer types in a plethora of preclinical studies. In breast cancer, melatonin is capable to disrupt estrogen-dependent cell signaling, resulting in a reduction of estrogen-stimulated cells, moreover, it's obvious neuro-immunomodulatory effect in organism was described. Several prospective studies have demonstrated the inverse correlation between melatonin metabolites and the risk of breast cancer. This correlation was confirmed by observational studies that found lower melatonin levels in breast cancer patients. Moreover, clinical studies have showed that circadian disruption of melatonin synthesis, specifically night shift work, is linked to increased breast cancer risk. In this regard, proper light/dark exposure with more selective use of light at night along with oral supplementation of melatonin may have benefits for high-risk women. The results of current preclinical studies, the mechanism of action, and clinical efficacy of melatonin in breast cancer are reviewed in this paper. Melatonin alone or in combined administration seems to be appropriate drug for the treatment of early stages of breast cancer with documented low toxicity over a wide range of doses. These and other issues are also discussed.

Adapted methods for scanning electron microscopy (SEM) in assessment of human sperm morphology.

Infertility is a widespread problem, and in some cases, the routine basic semen analysis is not sufficient to detect the cause of male infertility. The use of the scanning electron microscope (SEM) could provide a detailed insight into spermatozoa morphology, but it requires specific sample preparation techniques. The purpose of this study was to select, adjust, and optimize a method for the preparation of spermatozoa samples prior to SEM analysis, and to establish the protocol required for its use in clinical practice. We examined sperm samples of 50 men. The samples were fixed with modified iso-osmolar aldehyde solution followed by osmium post-fixation. In the first method, dehydration of the cells and subsequent critical point drying (CPD) were performed on a coverslip. In the second method, the samples were dehydrated in centrifuge tubes; hexamethyldisilazane (HMDS) was used as a drying agent instead of CPD, and the samples were air-dried. The third procedure was based on a membrane filter. The samples were dehydrated and dried with HMDS in a Gooch crucible, continuously, without centrifugation or redispersion of the sample. Our results showed that the fixation with modified iso-osmolar aldehyde solution followed by osmium post-fixation, and combined with dehydration and CPD on a coverslip, is the most convenient procedure for SEM sample preparation. In the case of small-size samples or low sperm concentration, dehydration and drying with HMDS on the membrane filter enabled the best reliability, repeatability, and comparability of the results. The presented procedures are suitable for routine use, and they can be applied to confirm as well as to correct a diagnosis.

Adipokines in neurovascular diseases.

Adipose tissue is now described as an endocrine organ secreting a number of adipokines contributing to the development of inflammation and metabolic imbalance, but also endothelial dysfunction, vascular remodeling, atherosclerosis, and ischemic stroke. Leptin, adiponectin, and resistin are the most studied adipokines which play important roles in the regulation of cardiovascular homeostasis. Leptin and adiponectin mediate both proatherogenic and antiatherogenic responses. Leptin and adiponectin have been linked to the development of coronary heart disease and may be involved in the underlying biological mechanism of ischemic stroke. Resistin, a pro-inflammatory cytokine, is predictive of atherosclerosis and poor clinical outcomes in patients with coronary artery disease and ischemic stroke. The changes in serum levels of novel adipokines apelin, visfatin are also associated with acute ischemic stroke. These adipokines have been proposed as potential prognostic biomarkers of cardiovascular mortality/morbidity and therapeutic targets in patients with cardiometabolic diseases. In this article, we summarize the biologic role of the adipokines and discuss the link between dysfunctional adipose tissue and metabolic/inflammation imbalance, consequently endothelial damage, progression of atherosclerotic disease, and the occurrence of ischemic stroke.