Associations of TNFA, IL17A, and RORC mRNA expression levels in peripheral blood leukocytes with obesity-related asthma in adolescents.

Obesity is associated with a unique non-T2 asthma phenotype, characterised by a Th17 immune response. Retinoid-related orphan receptor C (RORC) is the master transcription factor for Th17 polarisation. We investigated the association of TNFA, IL17A, and RORC mRNA expression levels with the non-T2 phenotype. We conducted a cross-sectional study in adolescents, subdivided as follows: healthy (HA), allergic asthma without obesity (AA), obesity without asthma (OB), and non-allergic asthma with obesity (NAO). TNFA, IL17A, and RORC mRNA expression in peripheral blood leukocytes were assessed by RT-PCR. NAO exhibited higher TNFA mRNA expression levels than HA or OB, as well as the highest IL17A and RORC mRNA expression levels among the four groups. The best biomarker for discriminating non-allergic asthma among obese adolescents was RORC mRNA expression levels (area under the curve: 0.95). RORC mRNA expression levels were associated with the non-T2 asthma phenotype, hinting at a therapeutic target in obesity-related asthma.

Modifications in GPR21 and GPR82 genes expression as a consequence of metabolic syndrome etiology.

Metabolic syndrome (MS) has been related with alterations in expression levels of orphan G protein coupled receptors (GPCRs) such as GPR21 and GPR82, which could be involved in some of the elements that characterizes the metabolic syndrome. The aim of this work was to evaluate changes in GPR21 and GPR82 receptors expression in two models of metabolic syndrome: one genetic (Zucker rats), and the other based on a diet (70% fructose for 9 weeks). GPR21 and GPR82 gene expressions were evaluated in brain, heart, aorta, liver and kidney by RT-qPCR. Rats with a high fructose diet, as well as obese Zucker rats, showed initial stages of pancreatic damage and alterations in some biochemical parameters related to the model consistent with the classification of MS. GPR21 and GPR82 receptors expressed in all tissues. The expression of GPR21 decreased in heart, aorta and kidney, but in liver the expression was different: decreased in diet model and increased in genetic model. In contrast, GPR82 expression depended of tissue and metabolic syndrome model. The results highlight the possible role of GPR21 and GPR82 receptors in the development MS. We conclude that the expression of GPR21 and GPR82 in different tissues is related with MS and depend of the origin of the syndrome, so they could be a therapeutic target for that syndrome.

Changes in expression of orphan receptors GPR99 and GPR107 during the development and establishment of hypertension in spontaneously hypertensive rats.

Hypertension is a disease, which in spite of existing treatments continues to have high morbidity and mortality, which suggests that there are other mechanisms involved in this pathology. In this sense, the orphan receptors are G protein-coupled receptor associated with various pathologies such as GPR99 which has been linked to mice develop left ventricular hypertrophy induced by blood pressure overload while GPR107 with patients with idiopathic pulmonary arterial hypertension. For this reason, the aim of this work was to study if the expression of the orphan receptors GPR99 and GPR107 are modified by arterial hypertension. Male SHR and WKY rats of 6-8 and 10-12 weeks old were used. The weight, systolic blood pressure and heart rate were measured, as well as the mRNA of the receptors GPR99 and GPR107 in the aorta, kidney, heart and brain by RT-PCR, also was realized an in silico analysis to predict which G protein could be coupled the orphan receptor GPR107. Our results showed that receptors GPR99 and GPR107 are expressed in the analyzed tissues and their expression profile tends to change at different ages and with the development of hypertension, for the other hand, the bioinformatics analysis for GPR107 showed that is coupled to Gi protein. Therefore, we do not rule out that GPR99 and GPR107 could be involved in the pathophysiology of hypertension and could be used as targets therapeutic in hypertension.

Retinol-binding protein 4 and plasminogen activator inhibitor-1 as potential prognostic biomarkers of non-allergic asthma caused by obesity in adolescents.

BACKGROUND: Non-allergic asthma caused by obesity is a complication of the low-grade chronic inflammation inherent in obesity. Consequently, the serum concentrations of adipokines such as retinol-binding protein 4 (RBP4) and plasminogen activator inhibitor-1 (PAI-1) increase. No gold standard molecule for the prediction of non-allergic asthma among obese patients has been identified. OBJECTIVE: To evaluate RBP4 and PAI-1 as prognostic biomarkers of non-allergic asthma caused by obesity. METHODS: A cross-sectional study between four groups of adolescents: (1) healthy (n = 35), (2) allergic asthma without obesity (n = 28), (3) obesity without asthma (n = 33), and (4) non-allergic asthma with obesity (n = 18). RESULTS: RBP4 was higher in the non-allergic asthma with obesity group than in the obesity without asthma group (39.2 ng/mL [95% confidence interval (CI): 23.8-76.0] vs. 23.5 ng/mL [95% CI: 3.2-33.5], p < 0.01), and PAI-1 was higher in the non-allergic asthma with obesity group than in the obesity without asthma group (21.9 ng/mL [95% CI: 15.7-26.5] vs. 15.9 ng/mL [95% CI: 9.4-18.2], p < 0.05). Receiver operating characteristic (ROC) curve analysis demonstrated that the serum RBP4 cut-off value was >42.78 ng/mL, with an area under the ROC curve (AUC) of 0.741 (95% CI: 0.599-0.853, p = 0.001), considered acceptable. The PAI-1 cut-off value was >12.0 ng/mL, with an AUC of 0.699 (95% CI: 0.554-0.819, p = 0.008), considered fair. CONCLUSIONS: RBP4 may be useful to predict non-allergic asthma among obese adolescents in clinical practice.

Silencing of GPR82 with Interference RNA Improved Metabolic Profiles in Rats with High Fructose Intake.

Metabolic syndrome (MS) is a clinical condition, constituted by alterations that lead to the onset of type II diabetes and cardiovascular disease. It has been reported that orphan G-protein-coupled receptor 82 (GPR82) participates in metabolic processes. The aim of this study was to evaluate the function of GPR82 in MS using a small interfering RNA (siRNA) against this receptor. We used Wistar rats of 10-12 weeks of age fed with a high-fructose solution (70%) for 9 weeks to induce MS. Subsequently, the rats were treated with an intrajugular dose of an siRNA against GPR82 and the effects were evaluated on day 3 and 7 after administration. On day 3 the siRNA had a transient effect on decreasing blood pressure and triglycerides and increasing high-density lipoprotein cholesterol, which recovered to the MS control on day 7. Decreased gene expressions of GPR82 mRNA in the aorta and heart were observed on day 3; moreover, decreased gene expression was maintained in the aorta on day 7. Therefore, we conclude that the orphan receptor GPR82 participates in the development of MS induced by fructose and the silencing of this receptor could ameliorate metabolic components.

Altered function and expression of the orphan GPR135 at the cardiovascular level in diabetic Wistar rats.

Cardiovascular complications are the main cause of mortality in patients with diabetes, these have been associated with changes in function and expression of receptors coupled to G proteins (GPCR), which include orphan receptors which some of them tend to modify in diabetes, although others are not known, such as GPR135. For this reason, the objective of this work was to study the expression of the orphan receptor GPR135 in brain, heart, kidney, aorta, lung, spleen and liver of diabetic rats, as well as its function by the administration of siRNA (small interfering RNA) and curves to isoproterenol. Our results showed that GPR135 is expressed in all tissues analyzed and its expression is modified due to diabetes, we also observed that the responses to isoproterenol increase in diabetic rats administered with siRNA. Therefore, we conclude that the orphan receptor GPR135 is expressed in different tissues and its expression tends to be modified due to diabetes, besides that it is functional and that it seems to be coupled to Gi/o protein which has negative chronotropic and inotropic effects, therefore, we do not rule out that it participates in the cardiovascular complications associated with diabetes.

Postnatal overnutrition affects metabolic and vascular function reflected by physiological and histological changes in the aorta of adult Wistar rats.

Rigorous nutritional care during early life leads to healthy adulthood. Cardiovascular and metabolic disorders, the most prevalent clinical challenges worldwide, are epidemiologically linked to poor nutritional habits throughout life. We aimed to understand whether postnatal overnutrition (PO) initiated during lactation affects metabolic markers and vascular function later in life. To test this hypothetical effect, we studied a PO Wistar rat model based on adjusting litter size at the third day of age to three pups and eight for the control group (C). Systemic parameters such as body weight and food intake were significantly increased in adult rats, measured up to 36 weeks. Moreover, fat mass, triglycerides, insulin and systolic blood pressure were all significantly increased in the PO group. Furthermore, we assessed whether these alterations would affect morphological and functional parameters in isolated vessels. Consistent with systemic alterations of the vasculature, contraction of thoracic aortic rings, determined by dose-response curves to norepinephrine (NE), was significantly reduced in PO rats. Histological stains revealed that the relative area of collagen was higher and the elastic fiber density was lower in the distal rings of PO rats. Altogether, our results highlight the critical importance of having a healthy neonatal nutrition to prevent harmful metabolic and vascular alterations during adulthood.

Evidence of alterations in the expression of orphan receptors GPR26 and GPR39 due to the etiology of the metabolic syndrome.

AIMS: Metabolic syndrome (MS) is composed of several metabolic abnormalities that increase the risk of cardiovascular diseases and diabetes. Although there are treatments for the components of MS, this pathology maintains a high mortality, suggesting that there are other mechanisms in which orphan receptors such as GPR26 and GPR39 may be involved. For this reason, the aim of this work was to evaluate the expression of GPR26 and GPR39 orphan receptors in two models of MS (diet and genetics). MATERIALS AND METHODS: We used male Wistar rats, which received 70% fructose in drinking water for 9 weeks, and obese Zucker rats. We measured weight, blood pressure, glucose, triglycerides, total cholesterol, HDL cholesterol, LDL cholesterol to determine the MS and the expression of the orphan receptors GPR26 and GPR39 in brain, heart, aorta, liver, and kidney by RT-PCR. RESULTS: The analysis of the expression of the orphan receptors GPR26 and GPR39 showed that the receptors are expressed in some tissues, but the expression of the GPR26 tends to decrease in the heart and aorta, whereas in the brain, no changes were observed, this receptor is not expressed in the liver and kidney of both strains. The expression of GPR39 isoforms depends on the tissue and MS model. CONCLUSIONS: We conclude that the orphan receptors GPR26, GPR39v1, and GPR39v2 are expressed in different tissues and their profile expression is dependent on the etiology of the MS.

Adipokines, asymmetrical dimethylarginine, and pulmonary function in adolescents with asthma and obesity.

OBJECTIVE: This study was to investigate whether the metabolic abnormalities of adipokines and asymmetrical dimethylarginine (ADMA) associate with pulmonary function deficits in adolescents with obesity and asthma. METHODS: This study enrolled 28 obese adolescents with asthma, 46 obese adolescents without asthma, 58 normal-weight adolescents with asthma, and 63 healthy control subjects. Serum levels of leptin, high-molecule-weight (HMW) adiponectin, retinol binding protein 4 (RBP4), asymmetrical dimethylarginine (ADMA), and pulmonary function were qualified. RESULTS: The obese subjects had higher levels of leptin and ADMA but lower levels of HMW adiponectin than the normal-weight subjects with or without asthma. The subjects with asthma had higher levels of RBP4 than those without asthma. The obese adolescents with asthma had lowest forced expiratory lung volume in the first second (FEV1)/forced vital capacity (FVC) ratio among the four study groups. In all the study subjects and in the subjects with asthma alone, the FEV1/FVC ratio associated negatively with leptin, however, such association was rendered non-significant when adjusted for BMI. The pulmonary function deficits associated inversely with BMI percentile in the subjects with asthma. However, the decreased FEV1/FVC ratio was not correlated with HMW adiponectin, RBP4 or ADMA. CONCLUSIONS: Our present study confirmed obstructive pattern of pulmonary function characterized by the reduced FEV1/FVC ratio in the obese adolescents with asthma. These pulmonary deficits were associated inversely with the increased BMI percentile.

Expression and localization of the AT1 and AT2 angiotensin II receptors and α1A and α1D adrenergic receptors in aorta of hypertensive and diabetic rats.

Hypertension and diabetes are multifactorial diseases that frequently coexist and exacerbate each another. During the development of diabetes, the impairment of noradrenergic and renin-angiotensin systems has been reported in the response mediated by α1-AR and AT1 receptors. Although their participation in the development of cardiovascular complications is still controversial, some studies have found increased or diminished response to the vasoconstrictive effect of noradrenaline or angiotensin II in a time-dependent manner of diabetes. Thus, the aim of this work was to investigate the possible changes in the expression or localization of α1-AR (α1A and α1D) and angiotensin II receptors (AT1 and AT2) in aorta of rats after 4 weeks of the onset of diabetes. In order to be able to examine the expression of these receptors, immunofluorescence procedure was performed in tunica intima and tunica media of histological sections of aorta. Fluorescence was detected by a confocal microscopy. Our results showed that the receptors are expressed in both tunics, where adrenergic receptors have a higher density in tunica intima and tunica media of SHR compared with WKY; meanwhile, the expression of angiotensin II receptors is not modified in both groups of rats. On the other hand, the results showed that diabetes produced an increase or a decrease in the expression of receptors that is not associated to a specific type of receptor, vascular region, or strain of rat. In conclusion, diabetes and hypertension modify the expression of the receptors in tunica intima and tunica media of aorta in a different way.

Abnormality of adipokines and endothelial dysfunction in Mexican obese adolescents with insulin resistance.

PURPOSE: The aim of this study was to investigate the possible relationship among insulin resistance (IR), endothelial dysfunction, and alteration of adipokines in Mexican obese adolescents and their association with metabolic syndrome (MetS). MATERIALS AND METHODS: Two hundred and twenty-seven adolescents were classified according to the body mass index (BMI) (control: N=104; obese: N=123) and homeostasis model of the assessment-insulin resistance index (HOMA-IR) (obese with IR: N=65). The circulating concentrations of leptin, adiponectin, soluble intercellular adhesion molecule-1 (sICAM-1), and IR were determined by standard methods. RESULTS: The obese adolescents with IR presented increased presence of MetS and higher circulating concentrations in sICAM-1 in comparison with the obese subjects without IR. The lowest concentrations of adiponectin were observed in the obese with IR. In multivariate linear regression models, sICAM-1 along with triglycerides, total cholesterol, and waist circumference was strongly associated with HOMA-IR (R2=0.457, P=0.008). Similarly, after adjustment for age, BMI-SDS, lipids, and adipokines, HOMA-IR remained associated with sICAM-1 (R2=0.372, P=0.008). BMI-SDS was mildly associated with leptin (R2=0.176, P=0.002) and the waist circumference was mild and independent determinant of adiponectin (R2=0.136, P=0.007). CONCLUSIONS: Our findings demonstrated that the obese adolescents, particularly the obese subjects with IR exhibited increased presence of MetS, abnormality of adipokines, and endothelial dysfunction. The significant interaction between IR and endothelial dysfunction may suggest a novel therapeutic approach to prevent or delay systemic IR and the genesis of cardiovascular diseases in obese patients.

Expression of orphan receptors GPR22 and GPR162 in streptozotocin-induced diabetic rats.

AIMS/INTRODUCTION: Diabetes mellitus is a chronic degenerative disease characterized by high blood glucose levels as a result of problems in the action or insulin secretion. Although there are many treatments for this pathology, it has been associated with a high mortality rate. For this reason, it is important to try to identify new pathways that could be involved in diabetic complications. Recently, a new class of receptors has been reported, called orphan receptors because the associated ligand and signaling pathways are unknown, these receptors have been associated with certain pathologies. Therefore, the aim of this work was to study the expression of the orphan receptors GPR22 and GPR162 in heart, aorta, brain and kidney of diabetic rats. MATERIALS AND METHODS: We used Wistar male rats with 10-12 weeks of age. Diabetes was induced by a single dose of streptozotocin (60 mg/kg i.p.). After four weeks, the tissue was obtained and the expression of the mRNA was measured by RT-PCR. RESULTS: Our results showed that the orphan receptors are expressed in a different way in heart, kidney, brain and aorta of diabetic and non-diabetic rats. CONCLUSIONS: We conclude that orphan receptors could be involved in the development of diabetes complications.

PPARα Stimulation Modulates Myocardial Ischemia-induced Activation of Renin-Angiotensin System.

We have recently demonstrated that peroxisome proliferator-activated receptor alpha (PPARα) stimulation lowers the production of angiotensin II while increasing the production of Ang-(1-7), both in cardiac and plasmatic level. This stimulation improves nitric oxide bioavailability, preserving cardiac histologic features and functioning. Based on these results, we decided to study the effect of PPARα stimulation on renin-angiotensin system components of ischemic myocardium. Male Wistar rats (weighing 300-350 g) were assigned to the following groups: (1) sham, (2) myocardial ischemia vehicle-treated (MI-V), and (3) myocardial ischemia clofibrate-treated. Expression of the angiotensin-converting enzyme increased during ischemia, whereas clofibrate-treated group remained comparable to control. Activation of the PPARα receptor stimulated the expression of angiotensin-converting enzyme-2; while the activity of this enzyme was increased in MI-V, clofibrate inhibited any change. The concentration of bradykinin and phospho-Akt(SER473) in homogenate increased in the animals treated with the drug. Mas receptor expression increased in MI-V rats. In conclusion, stimulation of PPARα by clofibrate prevents an increase in the activity of renin-angiotensin system and promotes the production of vasodilator substances.

Effect of six-month lifestyle intervention on adiponectin, resistin and soluble tumor necrosis factor-α receptors in obese adolescents.

The aim of this study was to evaluate the effect of a six-month lifestyle intervention on adiponectin, resistin, and two soluble forms of tumor necrosis factor-α receptor (sTNFR) in obese adolescents. A total of 54 obese adolescents aged 10 to 16 years completed the program. Twenty-four adolescents with normal weight at baseline were used as a control group. Our results demonstrated that obese adolescents had abnormal lipid profile, homeostasis model assessment (HOMA) index, adiponectin level (5.6 ± 2.7 vs. 7.6 ± 2.9 µg/mL, p = 0.005) as well as resistin level (31.0 ± 9.0 vs. 24.3 ± 8.5 ng/mL, p = 0.003), whereas levels of both sTNFRs were similar to those in normal weight subjects. After the six-month lifestyle intervention, obese adolescents had a slight but significant drop in standard deviation score-body mass index (SDS-BMI), a significant decrease in waist circumference, total cholesterol, triglycerides, HOMA index, as well as resistin, and a significant increase in adiponectin and high-density lipoprotein-cholesterol. In adolescents without decreased SDS-BMI, no change was observed in adipokines. Changes in adiponectin correlated negatively with changes in waist circumference (r = -0.275, p = 0.044). Changes in resistin correlated positively with changes in triglycerides (r = 0.302, p = 0.027). The study demonstrated the increase of resistin and the decrease of adiponectin in obese adolescents. Lifestyle intervention improved adipokine abnormalities in obese subjects.

Effect of Supplementation with Omega-3 Polyunsaturated Fatty Acids on Metabolic Modulators in Skeletal Muscle of Rats with an Obesogenic High-Fat Diet.

Previous studies provided evidence of the benefits of omega-3 polyunsaturated fatty acids (ω-3 PUFA) on the cardiovascular system and inflammation. However, its possible effect on skeletal muscle is unknown. This study aimed to evaluate whether ω-3 PUFA reverses the dysregulation of metabolic modulators in the skeletal muscle of rats on a high-fat obesogenic diet. For this purpose, an animal model was developed using male Wistar rats with a high-fat diet (HFD) and subsequently supplemented with ω-3 PUFA. Insulin resistance was assessed, and gene and protein expression of metabolism modulators in skeletal muscle was also calculated using PCR-RT and Western blot. Our results confirmed that in HFD rats, zoometric parameters and insulin resistance were increased compared to SD rats. Furthermore, we demonstrate reduced gene and protein expression of peroxisome proliferator-activated receptors (PPARs) and insulin signaling molecules. After ω-3 PUFA supplementation, we observed that glucose (24.34%), triglycerides (35.78%), and HOMA-IR (40.10%) were reduced, and QUICKI (12.16%) increased compared to HFD rats. Furthermore, in skeletal muscle, we detected increased gene and protein expression of PPAR-α, PPAR-γ, insulin receptor (INSR), insulin receptor substrate 1 (ISR-1), phosphatidylinositol-3-kinase (PI3K), and glucose transporter 4 (GLUT-4). These findings suggest that ω-3 PUFAs decrease insulin resistance of obese skeletal muscle.

siRNA Targeting ECE-1 Partially Reverses Pulmonary Arterial Hypertensionassociated Damage in a Monocrotaline Model.

AIMS: The aim of this study was to develop a possible treatment for pulmonary arterial hypertension. BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease characterised by a pulmonary arterial pressure greater than 20 mmHg. One of the factors that contribute to PAH is an increase in the production of endothelin-1, a polypeptide that increases vascular resistance in the pulmonary arteries, leading to increased pulmonary arterial pressure and right ventricular hypertrophy. OBJECTIVE: The objective of this study was to design, synthesize, and evaluate two siRNAs directed against endothelin-1 in a rat model of PAH induced with monocrotaline. METHODS: Wistar rats were administered monocrotaline (60 mg/kg) to induce a PAH model. Following two weeks of PAH evolution, the siRNAs were administered, and after two weeks, right ventricular hypertrophy was evaluated using the RV/LV+S ratio, blood pressure, weight, and relative expression of ECE-1 (Endothelin-converting enzyme-1) mRNA (messenger RNA) by RT-PCR (real-time PCR). RESULTS: The monocrotaline group showed an increase in the hypertrophy index and in ECE-1 mRNA, as well as a significant decrease in weight compared to the control group, while in the monocrotaline + siRNA group, a significant decrease was observed in the relative expression of ECE-1 mRNA, as well as in right ventricular hypertrophy. CONCLUSIONS: Based on the above information, we conclude that the administration of siRNAs directed to ECE-1 decreases the damage associated with PAH.

Hydrogen sulfide ameliorates hypertension and vascular dysfunction induced by insulin resistance in rats by reducing oxidative stress and activating eNOS.

Hydrogen sulfide (H2S) is a gasotransmitter implied in metabolic diseases, insulin resistance, obesity, and type 2 Diabetes Mellitus. This study aimed to determine the effect of chronic administration of sodium hydrosulfide (NaHS; inorganic H2S donor), L-Cysteine (L-Cys; substrate of H2S producing enzymes) and DL-Propargylglycine (DL-PAG; cystathionine-gamma-lyase inhibitor) on the vascular dysfunction induced by insulin resistance in rat thoracic aorta. For this purpose, 72 animals were divided into two main sets that received: 1) tap water (control group; n = 12); and 2) fructose 15% w/v in drinking water [insulin resistance group (IR); n = 60] for 20 weeks. After 16 weeks, the group 2 was divided into five subgroups (n = 12 each), which received daily i. p. injections during 4 weeks of: 1) non-treatment (control); 2) vehicle (phosphate buffer saline; PBS, 1 ml/kg); 3) NaHS (5.6 mg/kg); 4) L-Cys (300 mg/kg); and (5) DL-PAG (10 mg/kg). Hemodynamic variables, metabolic variables, vascular function, ROS levels and the expression of p-eNOS and eNOS were determined. IR induced: 1) hyperinsulinemia; 2) increased HOMA-index; 3) decreased Matsuda index; 4) hypertension, vascular dysfunction, increased ROS levels; 5) increased iNOS, and 6) decreased CSE, p-eNOS and eNOS expression. Furthermore, IR did not affect contractile responses to norepinephrine. Interestingly, NaHS and L-Cys treatment, reversed IR-induced impairments and DL-PAG treatment decreased and increased the HOMA and Matsuda index, respectively. Taken together, these results suggest that NaHS and L-Cys decrease the metabolic and vascular alterations induced by insulin resistance by reducing oxidative stress and activating eNOS. Thus, hydrogen sulfide may have a therapeutic application.

The Roles of MicroRNAs in Asthma and Emerging Insights into the Effects of Vitamin D3 Supplementation.

Asthma is one of the most common chronic non-communicable diseases worldwide, characterized by variable airflow limitation secondary to airway narrowing, airway wall thickening, and increased mucus resulting from chronic inflammation and airway remodeling. Current epidemiological studies reported that hypovitaminosis D is frequent in patients with asthma and is associated with worsening the disease and that supplementation with vitamin D3 improves asthma symptoms. However, despite several advances in the field, the molecular mechanisms of asthma have yet to be comprehensively understood. MicroRNAs play an important role in controlling several biological processes and their deregulation is implicated in diverse diseases, including asthma. Evidence supports that the dysregulation of miR-21, miR-27b, miR-145, miR-146a, and miR-155 leads to disbalance of Th1/Th2 cells, inflammation, and airway remodeling, resulting in exacerbation of asthma. This review addresses how these molecular mechanisms explain the development of asthma and its exacerbation and how vitamin D3 may modulate these microRNAs to improve asthma symptoms.

Effect of early diabetes on the expression of alpha-1 adrenergic receptors in aorta and carotid arteries of Wistar Kyoto and spontaneously hypertensive rats.

Hypertension and diabetes have been related to noradrenergic system impairment, especially to the response mediated by alpha-1 receptors. The aim of this work was to investigate possible changes in the expression of alpha-1 adrenergic receptors in aorta and carotid arteries of Wistar Kyoto and spontaneously hypertensive rats after 4 weeks of the onset of diabetes. Our results suggest that early diabetes modifies the expression of alpha-1 adrenergic receptors in aorta and carotid arteries of both WKY and SHR strains in a different way.

Clofibrate PPARα activation reduces oxidative stress and improves ultrastructure and ventricular hemodynamics in no-flow myocardial ischemia.

Peroxisome proliferator-activated receptors (PPAR) play a critical physiological role in energy homeostasis, in inflammation, and a protective role in cardiovascular function. We assessed the antioxidant effect of clofibrate-induced Peroxisome proliferator-activated receptor alpha (PPARα) stimulation on ischemic myocardium on myocardial morphology and hemodynamics. Male Wistar rats (300 g) were distributed into the following groups: (1) Sham, (2) myocardial ischemia vehicle treated (MI-V), and (3) myocardial ischemia clofibrate [100 mg/kg/ intraperitoneally) treated (MI-C). Reactive oxygen species (ROS) and lipid peroxidation increased in MI-V, whereas clofibrate prevented this effect. Superoxide dismutase (SOD)-1 and SOD-2 expression increased 4 times upon PPARα stimulation. SOD-1, SOD-2, and catalase activity also increased in response to clofibrate. eNOS mRNA and tetrahydrobiopterin increased in the MI-C group. Clofibrate was able to decrease Angiotensin II (AngII), AngII AT1-receptor, whereas Ang-(1-7) and AngII AT2-receptor expression increased. Assessment of myocardial morphology and cardiac function show that clofibrate improved histological features and hemodynamic parameters. Our results suggest that PPARα stimulation by clofibrate increases the antioxidant defense, leading to improved cardiac function.