In silico analysis and verification of critical genes related to vascular calcification in multiple diseases.

Identifying a functional molecular therapeutic target of vascular calcification (VC) that will not affect normal osteogenic differentiation is a challenge. To address this aim, we screened the differentially expressed genes (DEGs) in different VC conditions, including endothelial-osteogenic transition (EOT) (GSE167962), chronic kidney disease (CKD), and atherosclerosis (AS) (GSE159832). KEGG pathways, protein-protein interactions, and hub genes were also analyzed. The intersecting DEGs among the EOT, CKD, and AS groups were verified by quantitative reverse transcription polymerase chain reaction and immunohistochemistry in a DOCA-salt hypertension mouse model. The phosphoinositide 3-kinase-protein kinase B signaling pathway, ECM-receptor interaction, chemokine signaling pathway, and focal adhesion were enriched in EOT and AS-induced VC. ECM-receptor interaction, PPAR signaling pathway, apelin signaling pathway, AMPK signaling pathway, adipocytokine signaling pathway, and cholesterol metabolism were enriched in CKD and AS-induced VC. C4b, Cebpa, Lyz2, and Spp1 were also upregulated in EOT, CKD, AS, and hypertension. This study identified promising molecular targets for VC therapy.

Ultrathin Ti3C2Tx MXene sheets with high electrochemically active area anchored Pt boosting hydrogen evolution.

To reduce platinum usage, ultrathin MXene sheets with little restacking effect were prepared. The ultrathin MXene was prepared by a two-step etching process, which showed high specific surface area with low charge transfer resistance. The sample showed a double layer capacity of 64.98 mF cm-2, which is 14 times as large as that of ordinary HF prepared MXene, indicating a larger electrochemically active surface area. It showed a much better HER performance of ∼190 mV at 10 mA cm-2. The better performance attributes to 0.4 wt% Pt loaded. The Pt loaded MXene exhibited a better HER performance of ∼75 mV at 10 mA cm-2 and a Tafel slope of 61.7 mV·dec-1 close to 40 wt% commercial Pt/C. The sample performed better than Pt/C in a 3 h chronopotentiometry test and hardly changed in ECSA after the cyclic experiment. With more Pt loading, the sample delivered better HER performance than Pt/C in the LSV test (∼51 mV at 10 mA cm-2). This work provides an effective route for the preparation of ultrathin MXene sheets with larger electrochemically active area and more active sites for Pt loading, leading to superior HER performance.

Vaspin Alleviates Sepsis-Induced Cardiac Injury and Cardiac Inflammation by Inhibiting Kallikrein 7 in Mice.

Background: Vaspin is an important adipokine that is involved in cardiovascular diseases. This study is aimed at investigating whether vaspin participates in sepsis-induced cardiac injury and explored the possible mechanism. Methods: First, cecal ligation and puncture (CLP) and lipopolysaccharide (LPS) were used to establish a mouse model of sepsis, and cardiac vaspin expression was examined. In addition, after pretreatment with vaspin or phosphate-buffered saline (PBS), wild-type (WT) mice underwent CLP to establish a septic model and received sham as a control. Finally, WT mice and kallikrein 7 (KLK7-/-) mice were underwent CLP with or without vaspin pretreatment. Results: Mice that underwent CLP and were administered LPS exhibited increased vaspin expression in both the heart and serum compared with sham- or saline-treated mice. In CLP mice, pretreatment with vaspin reduced mortality and alleviated the expression of cardiac injury markers and cardiac dysfunction. In addition, vaspin reduced the cardiac levels of CD45+ cells and CD68+ cells, alleviated the cardiac inflammatory response, and reduced cardiomyocyte apoptosis. The protective effects of vaspin on CLP mice were masked by the deletion of KLK7, which was demonstrated to be a downstream signal of vaspin. Conclusions: Vaspin alleviates cardiac inflammation and plays a protective role in sepsis-induced cardiac injury by reducing KLK7 expression.

Actinobacteria Community and Their Antibacterial and Cytotoxic Activity on the Weizhou and Xieyang Volcanic Islands in the Beibu Gulf of China.

Weizhou Island and Xieyang Island are two large and young volcanic sea islands in the northern part of the South China Sea. In this study, high-throughput sequencing (HTS) of 16S rRNA genes was used to explore the diversity of Actinobacteria in the Weizhou and Xieyang Islands. Moreover, a traditional culture-dependent method was utilized to isolate Actinobacteria, and their antibacterial and cytotoxic activities were detected. The alpha diversity indices (ACE metric) of the overall bacterial communities for the larger island (Weizhou) were higher than those for the smaller island (Xieyang). A beta diversity analysis showed a more dispersive pattern of overall bacterial and actinobacterial communities on a larger island (Weizhou). At the order level, Frankiales, Propionibacteriales, Streptomycetales, Micrococcales, Pseudonocardiales, Micromonosporales, Glycomycetales, Corynebacteriales, and Streptosporangiales were the predominant Actinobacteria. A total of 22.7% of the OTUs shared 88%-95% similarity with some known groups. More interestingly, 15 OTUs formed a distinct and most predominant clade, and shared identities of less than 95% with any known families. This is the first report about this unknown group and their 16S rRNA sequences obtained from volcanic soils. A total of 268 actinobacterial strains were isolated by the culture-dependent method. Among them, 55 Streptomyces species were isolated, representing that 76.6% of the total. S. variabilis and S. flavogriseus were the most abundant. Moreover, some rare Actinobacteria were isolated. These included Micromonospora spp., Nocardia spp., Amycolatopsis spp., Tsukamurella spp., Mycobacterium spp., and Nonomuraea spp. Among them, eight Streptomyces spp. exhibited antibacterial activity against Bacillus cereus. Only three strains inhibited the growth of Escherichia coli. Four strains showed good activity against aquatic pathogenic bacterial strains of Streptococcus iniae. The cytotoxicity assay results showed that 27 strains (10.07%) exhibited cytotoxic activity against HeLa and A549 cell lines. Many actinobacterial strains with cytotoxic activity were identified as rare Actinobacteria, which illustrated that volcanic islands are vast reservoirs for Actinobacteria with promising antibacterial and cytotoxic activity. This study may significantly improve our understanding of actinobacterial communities on volcanic islands. The isolated Actinobacteria showed promising prospects for future use.

Corrigendum to "Anti-Interleukin-16-Neutralizing Antibody Attenuates Cardiac Inflammation and Protects against Cardiac Injury in Doxorubicin-Treated Mice".

[This corrects the article DOI: 10.1155/2021/6611085.].

Secreted frizzled-related protein 4 exerts anti-atherosclerotic effects by reducing inflammation and oxidative stress.

Atherosclerosis and its sequelae, such as coronary artery disease (CAD), are the most common diseases worldwide and the leading causes of morbidity and mortality in most countries. Our previous studies have shown that circulating secreted frizzled-related protein 4 (SFRP4) levels are increased in patients with CAD. However, the role of SFRP4 in the development of atherosclerosis remains unclear; thus, the purpose of this study was to determine the effect of SFRP4 on high-fat diet (HFD)-induced atherosclerosis and explore the possible mechanisms. In this study, we found for the first time that administration of recombinant SFRP4 alleviates atherosclerosis in ApoE-/- mice by reducing inflammation and oxidative stress. In addition, the anti-atherosclerotic effect of SFRP4 was associated with inhibition of the Wnt/ß-catenin signaling pathway, and Wnt1 overexpression abolished the anti-atherosclerotic effects of SFRP4. Taken together, our results highlight the potential beneficial effect of SFRP4 as a therapeutic agent for atherosclerosis and CAD.

Microbial communities in swamps of four mangrove reserves driven by interactions between physicochemical properties and microbe in the North Beibu Gulf, China.

Mangroves are distributed in coastal and estuarine regions and are characterized as a sink for terrestrial pollution. It is believed that complex interactions between environmental factors and microbial communities exist in mangrove swamps. However, little is known about environment-microbe interactions. There is a need to clarify some important environmental factors shaping microbial communities and how environmental factors interact with microbial assemblages in mangrove swamps. In the present study, physicochemical and microbial characteristics in four mangrove reserves (named ZZW, Qin, Bei, and GQ) in the North Beibu Gulf were determined. The interactions between environmental factors and microbial assemblages were analyzed with statistical methods in addition to CCA and RDA. Higher concentrations of sulfate (SO42--S) and Fe but lower concentrations of total phosphorus (TP) and NO3--N were detected in ZZW and Qin. Nutrient elements (NO3--N, NH4+-N, organic matter (OM), SO42--S, Fe, and TP) were more important than heavy metals for determining the microbial assemblages, and NO3--N was the most important factor. NO3--N, SO42--S, TP, and Fe formed a significant co-occurrence network in conjunction with some bacterial taxa, most of which were Proteobacteria. Notably, comparatively elevated amounts of sulfate-reducing bacteria (Desulfatibacillum, Desulfomonile, and Desulfatiglans) and sulfur-oxidizing bacteria (Thioprofundum and Thiohalophilus) were found in ZZW and Qin. The co-occurrence network suggested that some bacteria involved in sulfate reduction and sulfur oxidation drive the transformation of P and N, resulting in the reduction of P and N in mangrove swamps. Through the additional utilization of multivariate regression tree (MRT) and co-occurrence network analysis, our research provides a new perspective for understanding the interactions between environmental factors and microbial communities in mangroves.

Anti-Interleukin-16-Neutralizing Antibody Attenuates Cardiac Inflammation and Protects against Cardiac Injury in Doxorubicin-Treated Mice.

BACKGROUND: Interleukin-16 (IL-16) is an important inflammatory regulator and has been shown to have a powerful effect on the regulation of the inflammatory response. Cardiac inflammation has been reported to be closely related to doxorubicin- (DOX-) induced cardiac injury. In this study, the role of IL-16 in DOX-induced cardiac injury and the possible mechanisms were examined. METHODS: Cardiac IL-16 levels were first measured in DOX- or saline-treated mice. Additionally, mice were pretreated with the anti-IL-16-neutralizing antibody (nAb) or isotype IgG for 1 day and further administered DOX or saline for 5 days. Then, cardiac injury, cardiac M1 macrophage levels, and cardiomyocyte apoptosis were analyzed. The effects of the anti-IL-16 nAb on macrophage differentiation and cardiomyocyte apoptosis were also investigated in vitro. RESULTS: DOX administration increased IL-16 expression in cardiac macrophages compared with that of saline treatment. The anti-IL-16 nAb significantly decreased serum levels of lactate dehydrogenase (LDH), myocardial-bound creatine kinase (CK-MB), and cardiac troponin T (cTnT) and elevated cardiac function in DOX-induced mice. Treatment with the anti-IL-16 nAb also reduced p65 pathway activation, decreased M1 macrophage-related marker and cytokine expression, and protected against cardiomyocyte apoptosis in DOX-induced mice. In cell studies, the anti-IL-16 nAb also reduced DOX-induced M1 macrophage differentiation and alleviated apoptosis in cardiomyocytes cocultured with macrophages. CONCLUSIONS: The anti-IL-16 nAb protects against DOX-induced cardiac injury by reducing cardiac inflammation, and IL-16 may be a promising target to prevent DOX-related cardiac injury.

Interleukin-9 deficiency affects lipopolysaccharide-induced macrophage-related oxidative stress and myocardial cell apoptosis via the Nrf2 pathway both in vivo and in vitro.

Previous studies showed that interleukin-9 (IL-9) is involved in cardiovascular diseases, including hypertension and cardiac fibrosis. This study aimed to investigate the role of IL-9 in lipopolysaccharide (LPS)-induced myocardial cell (MC) apoptosis. Mice were treated with LPS, and IL-9 expression was measured and the results showed that compared with WT mice, LPS-treated mice exhibited increased cardiac Mø-derived IL-9. Additionally, the effects of IL-9 deficiency (IL-9-/-) on macrophage (Mø)-related oxidative stress and MC apoptosis were evaluated, the results showed that IL-9 knockout significantly exacerbated cardiac dysfunction, inhibited Nrf2 nuclear transfer, promoted an imbalance in M1 and M2 Møs, and exacerbated oxidative stress and MC apoptosis in LPS-treated mice. Treatment with ML385, a specific nuclear factor erythroid-2 related factor 2 (Nrf2) pathway inhibitor significantly alleviated the above effects in LPS-treated IL-9-/- mice. Bone marrow-derived Møs from wild-type (WT) mice and IL-9-/- mice were treated with LPS, and the differentiation and oxidative stress levels of Møs were measured. The effect of Mø differentiation on mouse MC apoptosis was also analyzed in vitro. The results showed that LPS-induced M1 Mø/M2 Mø imbalance and Mø-related oxidative stress were alleviated by IL-9 knockout but were exacerbated by ML385 treatment. The protective effects of IL-9 deficiency on the MC apoptosis mediated by LPS-treated Møs were reversed by ML-385. Our results suggest that deletion of IL-9 decreased the nuclear translocation of Nrf2 in Møs, which further aggravated Mø-related oxidative stress and MC apoptosis. IL-9 may be a target for the prevention of LPS-induced cardiac injury.

Anti-Interleukin-16 Neutralizing Antibody Treatment Alleviates Sepsis-Induced Cardiac Injury and Dysfunction via the Nuclear Factor Erythroid-2 Related Factor 2 Pathway in Mice.

Several interleukin (IL) members have been reported to participate in sepsis. In this study, the effects of IL-16 on sepsis-induced cardiac injury and dysfunction were examined, and the related mechanisms were detected. IL-16 expression in septic mice was first measured, and the results showed that both cardiac and serum IL-16 expression levels were increased in mice with sepsis induced by LPS or cecal ligation and puncture (CLP) compared with control mice. Then, IL-16 was neutralized, and the effects on lipopolysaccharide- (LPS-) induced cardiac injury were detected. The results showed that an anti-IL-16 neutralizing antibody (nAb) significantly reduced mortality and increased serum lactate dehydrogenase (LDH), creatine kinase myocardial bound (CK-MB), and cardiac troponin T (cTnT) levels while improving cardiac function in mice with LPS-induced sepsis. Neutralization of IL-16 also increased the activation of antioxidant pathways and the expression of antioxidant factors in septic mice while decreasing the activation of prooxidant pathways and the expression of prooxidants. Treatment with the anti-IL-16 nAb increased mitochondrial apoptosis-inducing factor (AIF) expression, decreased nuclear AIF and cleaved poly-ADP-ribose polymerase (PARP) expression, and decreased TUNEL-positive cell percentages in LPS-treated mice. Additionally, treatment with CPUY192018, the nuclear factor erythroid-2 related factor 2 (Nrf2) pathway, significantly increased mortality and reversed the above effects in mice treated with LPS and the anti-IL-16 nAb. Our results showed that the anti-IL-16 nAb regulates oxidative stress through the Nrf2 pathway and participates in the regulation of cardiac injury in septic mice. Neutralization of IL-16 may be a beneficial strategy for the prevention of cardiac injury and dysfunction in sepsis patients.

Diagnosis and treatment of eosinophilic myocarditis.

Eosinophilic myocarditis is a type of inflammatory cardiomyopathy characterized by eosinophilic infiltration into myocardial tissue. The accurate myocarditis incidence rate is difficult to determine because of the clinical limitations of an endomyocardial biopsy. The primary pathogenesis of eosinophilic myocarditis is the release of related substances by eosinophils, leading to cell membrane damage and cell destruction. However, evidence suggests that specific genes play a role in myocarditis development.As CMR imaging availability increases, the diagnosis rate of eosinophilic myocarditis will increase. The diagnosis of myocarditis mainly depends on an endocardial biopsy. Glucocorticoids can relieve patients' symptoms, but the early use of steroids may prevent intermediate disease stage development (i.e., thrombonecrosis and fibrosis with wall thrombosis). Anticoagulant therapy may also affect disease development. In addition to routine follow-up, a regular myocardial biopsy should be considered for discharged patients, if possible.

Interleukin-22 deficiency alleviates doxorubicin-induced oxidative stress and cardiac injury via the p38 MAPK/macrophage/Fizz3 axis in mice.

Several interleukin (IL) family members have been demonstrated to be involved in doxorubicin (DOX)-induced cardiac injury. This study aimed to investigate the role of IL-22 in DOX-induced cardiac injury and explore its possible mechanisms. In this study, mice were given DOX, and the cardiac expression and sources of IL-22 were determined. Then, IL-22 was knocked out to observe the effects on DOX-induced cardiac injury in mice. In addition, the p38 mitogen-activated protein kinase (MAPK) pathway was inhibited, macrophages were depleted and adoptively transferred, and Fizz3 was up-regulated in mice to explore the mechanisms. The results showed that cardiac IL-22 expression was significantly increased by DOX treatment and was mostly derived from cardiac macrophages. IL-22 knockout significantly reduced cardiac vacuolization and the expression of cardiomyocyte injury markers in both serum and left ventricular tissue and improved cardiac function in DOX-treated mice. In addition, IL-22 knockout reversed DOX-induced cardiac M1 macrophage/M2 macrophage imbalance, reduced oxidative stress and protected against cardiomyocyte apoptosis. p38 MAPK pathway inhibition with SB203580 and macrophage depletion further alleviated the above effects in DOX-treated IL-22-knockout mice. The effects were stronger IL-22-knockout mice with adoptive transfer of WT macrophages than in those with adoptive transfer of IL-22-knockout macrophages. Furthermore, increasing the expression of Fizz3 reduced cardiomyocyte apoptosis and alleviated cardiac dysfunction. Our results may suggest that IL-22 knockout alleviate DOX-induced oxidative stress and cardiac injury by inhibiting macrophage differentiation and thereby increasing the expression of Fizz3. Reductions in IL-22 expression may be beneficial for clinical chemotherapy in tumor patients.

ADAMTS-5 Decreases in Aortas and Plasma From Aortic Dissection Patients and Alleviates Angiotensin II-Induced Smooth Muscle-Cell Apoptosis.

Background: Acute aortic dissection (AAD) is associated with degeneration of the aortic media and accompanied by vascular extracellular matrix (ECM) remodeling. Recently, a disintegrin and metalloproteinase with thrombospondin type 1 motifs-5 (ADAMTS-5) has been reported to be involved in ECM remodeling and vascular diseases. The aim of this study was to examine ADAMTS-5 levels in AAD patients and investigate the underlying mechanisms. Methods: Aortic tissue samples were collected from normal donors and AAD patients, and the expression of ADAMTS-5 was analyzed in all aortic tissues. In addition, plasma levels of ADAMTS-5, matrix metalloproteinase (MMP)-2 and MMP-9, and tumor necrosis factor-α (TNF-α) were measured in repeated samples from AAD patients and compared to the non-AAD (NAD) group. In addition, we investigated the effects of ADAMTS-5 in smooth muscle cell (SMC) apoptosis. Results: The results showed that ADAMTS-5 expression was significantly reduced in the aortas of AAD patients and that SMCs were the main source of ADAMTS-5. In addition, the plasma ADAMTS-5 level was lower, but plasma MMP-2, MMP-9, and TNF-α levels were increased in the AAD patients. Multivariate linear regression analyses showed that a decreased ADAMTS-5 level in patients was independently associated with an increased risk of AAD. Furthermore, recombinant human ADAMTS-5 significantly ameliorated angiotensin (Ang II)-evoked SMC apoptosis. Conclusions: ADAMTS-5 shows promise as a novel potential biomarker for AAD, and regulation of SMC is a possible mechanism for the effects of ADAMTS-5.

Interleukin-22 is elevated in the atrium and plasma of patients with atrial fibrillation and increases collagen synthesis in transforming growth factor-ß1-treated cardiac fibroblasts via the JNK pathway.

Our previous studies demonstrated that interleukin (IL)-22 is involved in cardiovascular diseases such as hypertension, cardiac fibrosis and aortic dissection. The purpose of the present study was to detect IL-22 expression in patients with atrial fibrillation (AF). Atrial tissue was collected from donors with sinus rhythm and patients with permanent AF, and the expression level of IL-22 and its receptors (IL-22R1 and IL-10R2) in both the left atrium (LA) and right atrium (RA) of each sample was detected. Blood samples were also obtained from donors with paroxysmal, persistent and permanent AF and from donors without AF history, and IL-22 levels were measured. In addition, the effects of IL-22 on collagen synthesis in TGF-ß1-treated cardiac fibroblasts were investigated. IL-22R1, IL-10R2 and IL-22 expression was elevated in both the LA and RA in permanent AF patients. Elevated IL-22 expression positively correlated with the collagen areas and fibrosis marker levels in the atria of these patients. Plasma IL-22 levels were higher in AF patients compared with healthy donors and increased with increasing AF duration (from paroxysmal to persistent to permanent AF). A positive correlation was observed between IL-22 levels and TGF-ß1 levels in AF patients. In vitro, recombinant mouse IL-22 treatment upregulated α-SMA, collagen I and collagen III expression in TGF-ß1-treated cardiac fibroblasts. These effects were reversed by SP600125, an inhibitor of the JNK pathway. To conclude, IL-22 levels are elevated in patients with AF and may exacerbate collagen synthesis in TGF-ß1-induced cardiac fibroblasts. IL-22 may also influence AF by activating the JNK pathway.

IL-35 polymorphisms and cognitive decline did not show any association in patients with coronary heart disease over a 2-year period: A retrospective observational study (STROBE compliant).

Prior evidence suggested that inflammation and inflammatory cytokines polymorphisms might be essential in the development of coronary heart disease (CHD) and cognitive decline. The following study investigated the associations between interleukin-35 (IL-35) polymorphisms and cognitive decline in CHD patients over a 2-year period.CHD patients were enrolled between January 2015 and January 2016. Cognitive function, including memory, orientation, verbal and attention were assessed using Telephone Interview for Cognitive Status-Modified (TICS-m) during a 2-year follow-up. Genotypes of the single nucleotide polymorphisms (SNPs), including rs2243115, rs568408, rs582054, rs583911, rs428253, rs4740 and rs393581 of IL-35 were examined by MassArray (Sequenom). The differences of TICS-m score between 2-year interval were used to estimate the cognitive decline; linear regression model was used to analyze the association between IL-35 polymorphisms and cognitive decline in CHD patients after a 2-year follow-up.The mean age of study individuals was 60.58 (±7.86) years old. There were 255 (68.5%) males and 117 (31.5%) female patients. The TICS-m scores, including overall cognition score, verbal attention and memory scores gradually decreased over a 2 year follow up period (P < .001, respectively), whereas there was no difference in orientation function score between the 1-year and 2-year follow-up (P = .448). Furthermore, after adjusting for age, sex, history of hypertension(HT) and Diabetes mellitus(DM), smoking, education, Therapy regimen (PCI, CABG, medication) left ventricular ejection fraction (LVEF), and the severity of coronary artery stenosis (Gensini score), no association was found between IL-35 rs2243115, rs568408, rs582054, rs583911, rs428253, rs4740 genotypes and cognitive decline in CHD patients over a 2-year period.Our data reveled that IL-35 polymorphisms was not associated with cognitive decline in CHD patients over a 2-year period. Yet, further studies are needed to confirm the role of cytokine gene polymorphisms in cognitive decline among CHD patients.

Circulating Sestrin Levels Are Increased in Hypertension Patients.

BACKGROUND: Sestrins (Sesns), a group of oxidative stress-related proteins, have been reported to be involved in various cardiovascular diseases, including aortic dissection and chronic heart failure. This study is aimed at investigating the level of circulating Sesn1, Sesn2, and Sesn3 in hypertension patients. METHODS: Plasma levels of Sesn1, Sesn2, and Sesn3 in 400 hypertensive patients and 100 normotensive subjects were detected using enzyme-linked immunosorbent assay (ELISA) kits. The hypertension patients were divided into groups with grade I (n = 140), grade II (n = 180), and grade III (n = 80) hypertension. RESULTS: Compared with the normotensive subjects, Sesn1, Sesn2, and Sesn3 levels were increased in patients with hypertension, with a gradual increase between the groups with grade I, grade II, and grade III hypertension. Elevated Sesn1, Sesn2, and Sesn3 levels were positively correlated with both the systolic blood pressure (SBP) and diastolic blood pressure (DBP). Moreover, Sesn1, Sesn2, and Sesn3 levels were elevated in patients with dipper hypertension and further increased in patients with nondipper hypertension. In addition, smokers, as well as patients with higher levels of angiotensin II (Ang II) and carotid atherosclerotic plaque (CAP), exhibited increased Sesn1, Sesn2, and Sesn3 levels when compared with patients without these clinical characteristics. Furthermore, plasma levels of Sesn1, Sesn2, and Sesn3 were negatively correlated with the presence of CAP. CONCLUSIONS: Circulating Sesn levels are increased in patients with hypertension and may be a target for the prevention and treatment of clinical hypertension.

A single-center observational study on the expression of circulating interleukin-20 levels and predicting outcomes in human chronic heart failure: A 2-year follow-up cohort study: Higher IL-20 levels suggest poorer outcomes in CHF patients.

BACKGROUND: Interleukin-20 (IL-20) is closely related to cardiovascular diseases such as atherosclerosis. The relevance of IL-20 expression in human chronic heart failure (CHF) remains unknown. Thus, we investigated the level of circulating IL-20 in CHF patients and observed its correlation with CHF outcomes. METHODS: A cohort study was performed with CHF patients. Blood samples of 180 CHF patients and 167 control subjects were collected, and the plasma IL-20 level of each patient was determined. In addition, the endpoints of cardiovascular events among the CHF patients were evaluated prospectively. The maximum follow-up time of these CHF patients was 24 months, and the median follow-up time was 21 months. RESULTS: IL-20 levels were high in CHF patients and gradually increased in the New York Heart Association (NYHA) functional class II, the NYHA III and the NYHA IV groups. According to the low, middle and high tertiles of IL-20 levels, the CHF patients were respectively divided into groups 1, groups 2, and groups 3. Multivariate Cox hazard analysis showed that the group 3 exhibited significantly higher cardiac event morbidity than the other two groups after adjustment for confounding factors. The CHF patients were also divided into two groups according to plasma IL-20 levels, and higher rates of cardiovascular events were observed in the group with higher IL-20 levels. CONCLUSIONS: Circulating IL-20 levels are significantly elevated in CHF patients, and higher IL-20 levels suggest poorer outcomes in CHF patients.

The Expression of IL-12 Family Members in Patients with Hypertension and Its Association with the Occurrence of Carotid Atherosclerosis.

BACKGROUND: The interleukin-12 (IL-12) family consists of four members, namely, IL-12, IL-23, IL-27, and IL-35. The aim of this study was to examine the expression of circulating IL-12, IL-23, IL-27, and IL-35 in hypertensive patients. METHODS: Blood samples were collected from hypertensive patients and nonhypertensive (control) subjects, and protein multifactorial monitor kits were used to measure the plasma IL-12, IL-23, IL-27, and IL-35 levels in each sample. In addition, all enrolled subjects underwent ambulatory blood pressure monitoring (ABPM) and vascular stiffness. RESULTS: Hypertensive patients exhibited higher IL-12, IL-23, and IL-27 levels and lower IL-35 levels than control subjects; IL-12, IL-23, and IL-27 levels were positively correlated with both systolic blood pressure (SBP) and diastolic blood pressure (DBP), while IL-35 levels were negatively correlated with SBP and DBP. IL-12, IL-23, and IL-27 levels gradually increased in patients with grade I, II, and III hypertension, while IL-35 levels gradually reduced. According to the ABPM results, hypertensive patients were divided into the dipper and nondipper hypertension groups; IL-12, IL-23, IL-27, and IL-35 levels showed no differences between the two groups, but IL-12, IL-23, and IL-27 levels in both groups increased compared with those in the control group, while IL-35 levels decreased. Additionally, the expression of these IL-12 family members was influenced by many clinical factors and was independently associated with the occurrence of carotid atherosclerotic plaques. CONCLUSIONS: The changes in IL-12, IL-23, IL-27, and IL-35 levels were not associated with the presence of the nondipper type but were closely associated with the development of carotid atherosclerotic plaque in hypertensive patients.

Roles and Mechanisms of Interleukin-12 Family Members in Cardiovascular Diseases: Opportunities and Challenges.

Cardiovascular diseases represent a complex group of clinical syndromes caused by a variety of interacting pathological factors. They include the most extensive disease population and rank first in all-cause mortality worldwide. Accumulating evidence demonstrates that cytokines play critical roles in the presence and development of cardiovascular diseases. Interleukin-12 family members, including IL-12, IL-23, IL-27 and IL-35, are a class of cytokines that regulate a variety of biological effects; they are closely related to the progression of various cardiovascular diseases, including atherosclerosis, hypertension, aortic dissection, cardiac hypertrophy, myocardial infarction, and acute cardiac injury. This paper mainly discusses the role of IL-12 family members in cardiovascular diseases, and the molecular and cellular mechanisms potentially involved in their action in order to identify possible intervention targets for the prevention and clinical treatment of cardiovascular diseases.