Lessons Learned from a Global Perspective of Coronavirus Disease-2019.

Coronavirus disease-2019 has impacted the world globally. Countries and health care organizations across the globe responded to this unprecedented public health crisis in a varied manner in terms of public health and social measures, vaccination development and rollout, the conduct of research, developments of therapeutics, sharing of information, and in how they continue to deal with the widespread aftermath. This article reviews the various elements of the global response to the pandemic, focusing on the lessons learned and strategies to consider during future pandemics.

Effect of pecan nuts and extra-virgin olive oil on glycemic profile and nontraditional anthropometric indexes in patients with coronary artery disease: a randomized clinical trial.

BACKGROUND/OBJECTIVES: The influence of cardioprotective foods on nontraditional indexes related to dysglycemia and body fat distribution is unknown in individuals with coronary artery disease (CAD). This study aimed to evaluate the effect of a healthy diet supplemented with pecan nuts or extra-virgin olive oil on glycemic profile and adipose tissue dysfunction assessed by anthropometric indexes in patients with stable CAD. SUBJECTS/METHODS: In a randomized, pragmatic, parallel clinical trial lasting 12 weeks, 204 individuals were allocated to three interventions: a healthy diet (control group [CG], n = 67), a healthy diet plus 30 g/day of pecan nuts (pecan nut group [PNG], n = 68), or a healthy diet plus 30 mL/day of extra-virgin olive oil (olive oil group [OOG], n = 69). Triglyceride-glucose (TyG) index (primary outcome) and other markers of glycemic profile were evaluated, and nontraditional anthropometric indexes as well. Diet quality was assessed according to the Alternate Healthy Eating Index (mAHEI). RESULTS: After adjustment for baseline values, use of antidiabetic drugs and insulin, there were no differences in both glycemic and anthropometric profiles according to groups at the end of the study. PNG improved the quality of the diet in comparison to other groups (final mAHEI scores: CG: 19 ± 7.5; PNG: 26 ± 8; OOG: 18.9 ± 6; P < 0.001). CONCLUSIONS: There was no difference regarding glycemic and anthropometric parameters according to interventions in patients with stable CAD. However, adding pecan nuts to a healthy diet may improve its quality. Further studies must be conducted considering dietary interventions on secondary cardiovascular prevention setting. CLINICAL TRIALS IDENTIFIER NUMBER: NCT02202265. First Posted: July 2014; Last Update: September 2020.

Effects of supplementing a healthy diet with pecan nuts or extra-virgin olive oil on inflammatory profile of patients with stable coronary artery disease: a randomised clinical trial.

The consumption of nuts and extra-virgin olive oil has been associated with suppression of inflammatory pathways that contribute to atherosclerosis, but its role on the modulation of the inflammatory profile in patients with established coronary artery disease (CAD) is unclear. The aim of this study was to evaluate the effects of adding pecan nuts or extra-virgin olive oil to a healthy diet on inflammatory markers in patients with stable CAD. In this randomised clinical trial, 204 patients were enrolled to three study groups: sixty seven to control group (CG: healthy diet), sixty eight to pecan nuts group (PNG: 30 g/d of pecans + healthy diet) and sixty nine to extra-virgin olive oil group (OOG: 30 ml/d of extra-virgin olive oil + healthy diet). High-sensitivity C-reactive protein (hs-CRP, in mg/l), fibrinogen (mg/dl), IL 2, 4, 6, 10 (pg/ml) and interferon-γ (IFN-γ, in pg/ml), IL-6/IL-10, IL-2/IL-4 and IFN-/γIL-4 ratios were evaluated at baseline and after the follow-up (12 weeks). As main results, after adjustment for sex, statin used and relative body weight variation, there were no differences between groups regarding inflammatory markers at the end of the study. IL-6 levels (primary outcome) were reduced in 12 weeks when compared with baseline in all study groups (CG: difference: -0·593 (se = 0·159) pg/dL; PNG: difference: -0·335 (se = 0·143) pg/dl; OOG: IL-6 difference: -0·325 (se = 0·143) pg/dl). In conclusion, there was no significant effect of including pecan nuts or extra virgin olive oil to a healthy diet on inflammatory markers in individuals with CAD.

Effects of extra virgin olive oil and pecans on plasma fatty acids in patients with stable coronary artery disease.

OBJECTIVE: The aim of this study was to determine the effects of a healthy diet supplemented with extra virgin olive oil or pecans on plasma fatty acids (PFAs) in patients with stable coronary artery disease (CAD). METHODS: Patients 40 to 80 y of age were randomized to one of three dietary interventions (allocation ratio 1: 1: 1): healthy diet based on guidelines (control group [CG]), healthy diet supplemented with 30 g/d of pecans (PNG), or a healthy diet supplemented with 30 mL/d of extra virgin olive oil (OOG). PFAs were identified at baseline and at the end of follow-up (12 wk), and correlations between dietary fatty acids intake, PFAs, and clinical biomarkers of the lipid profile were also assessed before and after the interventions. RESULTS: Among 149 participants included in the analysis (43 CG; 51 PNG; and 55 OOG), correlations were observed between food intake, PFAs, and lipid profile before and after interventions independent of statins used, but all were considered weak. At the end of the study, the OOG showed increased concentrations of oleic fatty acid independently of the type of statin in use (1.49%; 95% confidence interval, 0.08-2.89; P = 0.029); however, there were no significant differences between the groups regarding the final mean values of oleic fatty acid or in the other PFAs. CONCLUSIONS: In patients with stable CAD, there were no significant differences in PFAs after 12 wk according to dietary interventions evaluated.

Maternal ingestion of cocoa causes constriction of fetal ductus arteriosus in rats.

Maternal consumption of polyphenol-rich foods has been associated with fetal ductus arteriosus constriction (DAC), but safety of chocolate exposure in fetal life has not been studied. This experimental study tested the hypothesis that maternal cocoa consumption in late pregnancy causes fetal DAC, with possible associated antioxidant effects. Pregnant Wistar rats, at the 21st gestational day, received by orogastric tube cocoa (720 mg/Kg) for 12 h, indomethacin (10 mg/Kg), for 8 h, or only water, before cesaren section. Immediately after withdrawal, every thorax was obtained and tissues were fixed and stained for histological analysis. The ratio of the narrowest part of the pulmonary artery to the fetal ductus inner diameter and increased ductal inner wall thickness characterized ductal constriction. Substances reactive to thiobarbituric acid were quantified. Statistical analysis used ANOVA and Tukey test. Cocoa (n = 33) and indomethacin (n = 7) reduced fetal internal ductus diameter when compared to control (water, n = 25) (p < 0.001) and cocoa alone increased ductus wall thickness (p < 0.001), but no change was noted in enzymes activity. This pharmacological study shows supporting evidences that there is a cause and effect relationship between maternal consumption of cocoa and fetal ductus arteriosus constriction. Habitual widespread use of chocolate during gestation could account for undetected ductus constriction and its potentially severe consequences, such as perinatal pulmonary hypertension, cardiac failure and even death. For this reason, dietary guidance in late pregnancy to avoid high chocolate intake, to prevent fetal ductal constriction, may represent the main translational aspect of this study.

Nutritional status and appetite-regulating hormones in early treatment of acute lymphoblastic leukemia among children and adolescents: a cohort study.

BACKGROUND: Children with acute lymphoblastic leukemia are at risk of malnutrition, but few studies have described the changes in nutritional status during the different phases of chemotherapy. OBJECTIVE: To evaluate changes in nutritional status, food intake and appetite-regulating hormones among children and adolescents with acute lymphoblastic leukemia in the first phase of chemotherapy. DESIGN AND SETTING: Cohort study developed in the pediatric oncology departments of two hospitals in the city of Natal, Rio Grande do Norte, Brazil. METHODS: Fourteen children/adolescents (mean age of 7 years; 50% female) with acute lymphoblastic leukemia were monitored over the 28 days of an induction chemotherapy cycle. Anthropometric measurements, 24-hours food weight records and appetite-regulating hormone levels (ghrelin, leptin, insulin and cortisol) were obtained at three different times (before, in the middle and at the end of the induction phase). RESULTS: Most of the patients (85.7%) had normal weight at the beginning of the treatment, and this did not change significantly during the 28 days. Energy and nutrient intakes improved from the start of the treatment to the midpoint, according to the ghrelin levels (from 511.1 ± 8.3 to 519.3 ± 6.6 pg/ml; P = 0.027). Other appetite-regulating hormones did not present changes. CONCLUSION: Food consumption improves during the first phase of treatment, without alterations in anthropometric nutritional status.

Adaptations in GLUT4 Expression in Response to Exercise Detraining Linked to Downregulation of Insulin-Dependent Pathways in Cardiac but not in Skeletal Muscle Tissue.

Insulin resistance is associated with cardiometabolic risk factors, and exercise training can improve insulin-mediated glucose uptake. However, few studies have demonstrated the reversibility of exercise-induced benefits. Thus, the authors examine the time-response effects of exercise training and detraining on glucose transporter 4 (GLUT4) content, insulin-dependent and insulin-independent pathways in cardiac and gastrocnemius muscle tissues of spontaneously hypertensive rats. Thirty-two male spontaneously hypertensive rats, 4 months old, were assigned to (n = 8/group): T (exercise training: 10-week treadmill exercise, 50-70% maximum effort capacity, 1 hr/day, 5 days/week); D2 (exercise training + 2-day detraining), D4 (exercise training + 4-day detraining); and S (no exercise). The authors evaluated insulin resistance, maximum effort capacity, GLUT4 content, p-IRS-1Tyr1179, p-AS160Ser588, p-AMPKα1Thr172, and p-CaMKIIThr286 in cardiac and gastrocnemius muscle tissues (Western blot). In response to exercise training, there were improvements in insulin resistance (15.4%; p = .010), increased GLUT4 content (microsomal, 29.4%; p = .012; plasma membrane, 27.1%; p < .001), p-IRS-1 (42.2%; p < .001), p-AS160 (60.0%; p < .001) in cardiac tissue, and increased GLUT4 content (microsomal, 29.4%; p = .009; plasma membrane, 55.5%; p < .001), p-IRS-1 (28.1%; p = .018), p-AS160 (76.0%; p < .001), p-AMPK-α1 (37.5%; p = .026), and p-CaMKII (30.0%; p = .040) in the gastrocnemius tissue. In D4 group, the exercise-induced increase in GLUT4 was reversed (plasma membrane, -21.3%; p = .027), p-IRS1 (-37.1%; p = .008), and p-AS160 (-82.6%; p < .001) in the cardiac tissue; p-AS160 expression (-35.7%; p = .034) was reduced in the gastrocnemius. In conclusion, the cardiac tissue is more susceptible to exercise adaptations in the GLUT4 content and signaling pathways than the gastrocnemius muscle. This finding may be explained by particular characteristics of insulin-dependent and insulin-independent pathways in the muscle tissues studied.

Nutritional status and appetite-regulating hormones in early treatment of acute lymphoblastic leukemia among children and adolescents: a cohort study

ABSTRACT BACKGROUND: Children with acute lymphoblastic leukemia are at risk of malnutrition, but few studies have described the changes in nutritional status during the different phases of chemotherapy. OBJECTIVE: To evaluate changes in nutritional status, food intake and appetite-regulating hormones among children and adolescents with acute lymphoblastic leukemia in the first phase of chemotherapy. DESIGN AND SETTING: Cohort study developed in the pediatric oncology departments of two hospitals in the city of Natal, Rio Grande do Norte, Brazil. METHODS: Fourteen children/adolescents (mean age of 7 years; 50% female) with acute lymphoblastic leukemia were monitored over the 28 days of an induction chemotherapy cycle. Anthropometric measurements, 24-hours food weight records and appetite-regulating hormone levels (ghrelin, leptin, insulin and cortisol) were obtained at three different times (before, in the middle and at the end of the induction phase). RESULTS: Most of the patients (85.7%) had normal weight at the beginning of the treatment, and this did not change significantly during the 28 days. Energy and nutrient intakes improved from the start of the treatment to the midpoint, according to the ghrelin levels (from 511.1 ± 8.3 to 519.3 ± 6.6 pg/ml; P = 0.027). Other appetite-regulating hormones did not present changes. CONCLUSION: Food consumption improves during the first phase of treatment, without alterations in anthropometric nutritional status.

Gene therapy for refractory angina and cell therapy for heart failure: experience of a Brazilian research group.

Cell therapy has shown impressive effects in experimental cardiomyopathy models. To a lesser extent, gene therapy has also been studied. In both cases, translation to clinical therapy has been disappointing. This paper is intended to describe the experience and achievements of a multicenter working group located in Porto Alegre, southern Brazil, in experimental and translational research projects for cell-based and gene therapy methods in the treatment of dilated and ischemic cardiomyopathies. The results of preclinical and clinical studies showed that bone marrow mononuclear stem cells indeed have an effect in improving myocardial perfusion and contractile function, but the overall results are poorly translated to the clinical level. Gene therapy studies with direct myocardial injections of naked VEGF 165 plasmid showed improvement in myocardial perfusion and function in animal models. A randomized clinical trial found that this method is safe and improved myocardial perfusion, but the benefits disappeared after 1 year. An animal experiment associating VEGF 165 with angiopoietin was undertaken in mini pigs to extend the durability of that therapy. In conclusion, our efforts to better understand the mechanisms and functions of gene and cell-based therapies in cardiology resulted in significant findings and propose a future look at cell-free therapeutic approaches.

Physical training prior to myocardial infarction potentializes stem cell therapy, SDF-1/CXCR4 axis activation and inhibits the vasoconstrictor response in hypertensive rats.

Stem cell therapy is a promising strategy for recovering of injured cardiac tissue after acute myocardial infarction. The effects promoted by preventive physical training, beneficial for regeneration, are not yet understood on stem cell homing. In the present study, we evaluated the effect of preventive physical training on cell homing activation and associated mechanisms after acute myocardial infarction and therapy with adipose-derived stem cells in spontaneously hypertensive rats (SHR). Forty female SHR were allocated in sedentary (S), sedentary SHAM (S-SHAM), sedentary AMI (S-AMI), sedentary with cell therapy (S-ICT), aerobically trained (T), trained SHAM (T-SHAM), trained AMI (T-AMI) and trained with cell therapy (S-ICT) groups. Cell therapy was performed through the infusion of 2 × 105 ADSC/0.05 mL at the moment of AMI. Molecular markers of cell homing (SDF-1/CXCR4), inflammatory response (myeloperoxidase and cardiac expression of iNOS, gp91phox and NFkB), vasoconstrictor agents (Ang II and ET-1) and an angiogenesis inducer (VEGF) were measured. Functional capacity and echocardiographic parameters were also evaluated. Preventive physical training associated with cell therapy was able to reduce left ventricle ejection fraction losses in infarcted animals. Results demonstrated activation of the SDF-1/CXCR4 axis by physical training, besides a reduction in vasoconstrictor and systemic inflammatory responses. Physical training prior to AMI was able to induce a cardioprotective effect and optimize the reparative mechanism of cell therapy in an animal model of hypertension.

Treating periodontal disease in patients with myocardial infarction: A randomized clinical trial.

BACKGROUND: Periodontitis has been associated with coronary artery disease, but the impact of a periodontal treatment on the endothelial function of patients with a recent ST-segment elevation myocardial infarction (STEMI) was not investigated. METHODS: Randomized controlled trial (NCT02543502). Patients admitted between August 2012 and January 2015 were included. Patients were screened during the index hospitalization for STEMI, and those with severe periodontal disease were randomized 2 weeks later to periodontal treatment or to control. The primary endpoint of this trial was the between group difference in the variation of flow-mediated vasodilation (FMD) in the brachial artery assessed by ultrasound from baseline to the 6-month follow-up. Secondary outcomes were cardiovascular events, adverse effects of periodontal treatment and inflammatory markers. RESULTS: Baseline characteristics were balanced between patients in the intervention (n = 24) and control groups (n = 24). There was a significant FMD improvement in the intervention group (3.05%; p = .01), but not in the control group (-0.29%; p = .79) (p = .03 for the intergroup comparison). Periodontal treatment was not associated with any adverse events and the inflammatory profile and cardiovascular events were not significantly different between both groups. CONCLUSIONS: Treatment of periodontal disease improves the endothelial function of patients with a recent myocardial infarction, without adverse clinical events. Larger trials are needed to assess the benefit of periodontal treatment on clinical outcomes. CLINICAL TRIAL REGISTRATION: NCT02543502 (https://clinicaltrials.gov/ct2/show/NCT02543502?term=NCT02543502&rank=1).

Effects of myocardial infarction and an intensive exercise bout on kinetic of lactate, and LDH-B levels in spontaneously hypertensive rats

Aims: This study aimed to evaluate the kinetics of lactate and lactate dehydrogenase B (LDH-B) protein levels as well as the maximum effort capacity of spontaneously hypertensive rats (SHRs) with experimental acute myocardial infarction (AMI). Methods: thirty-two SHRs were divided into (n=8/group): S (sham), SE (sham+exercise), I (AMI), and IE (AMI+exercise). A maximum exercise test (treadmill) was evaluated before AMI or sham surgery. Echocardiography was performed 48h after the surgery. Lactacidemia was assessed at rest and during an intense exercise bout (48h after echocardiography). A two-way ANOVA followed by the post-hoc (Bonferroni) test was used, p<0.05. Results: In the end, the heart was removed for analysis of LDH-B. AMI resulted in lower cardiac output (S vs I: ∆51.3%, p<0.001), ejection fraction (S vs I: ∆60.5%, p<0.001) and shortening fraction (S vs I: ∆72.4%, p<0.001). The IE showed a reduction in exercise capacity when compared with pre-AMI values (1.50±0.1 vs 1.38±0.2 km/h; p=0.030) but not when compared with SE (1.41±0.3 vs 1.38±0.2 km/h; p=0.208). During the exhaustion exercise session, IE group showed lower lactacidemia at 12 min (∆9.7%, p=0.042) and 18 min (∆8.3%, p=0.038). No differences were observed in the protein level of LDH-B among the groups (p=0.573). However, when the AMI factor was considered alone, LDH-B expression was lower (sham vs AMI rats, p=0.040). Conclusion: LDH-B protein levels in cardiac tissue appear to be associated with AMI only. Furthermore, AMI induced a reduction in exercise capacity but did not affect lactacidemia during the intense exercise bout.(AU)

Short-term exercise training improves cardiac function associated to a better antioxidant response and lower type 3 iodothyronine deiodinase activity after myocardial infarction.

AIMS: We assessed the effects of a short-term exercise training on cardiac function, oxidative stress markers, and type 3 iodothyronine deiodinase (D3) activity in cardiac tissue of spontaneously hypertensive rats (SHR) following experimental myocardial infarction (MI). METHODS: Twenty-four SHR (aged 3 months) were allocated to 4 groups: sham+sedentary, sham+trained, MI+sedentary and MI+trained. MI was performed by permanent ligation of the coronary artery. Exercise training (treadmill) started 96 hours after MI and lasted for 4 weeks (~60% maximum effort, 4x/week and 40 min/day). Cardiac function (echocardiography), thioredoxin reductase (TRx), total carbonyl levels, among other oxidative stress markers and D3 activity were measured. A Generalized Estimating Equation was used, followed by Bonferroni's test (p<0.05). RESULTS: MI resulted in an increase in left ventricular mass (p = 0.002) with decreased cardiac output (~22.0%, p = 0.047) and decreased ejection fraction (~41%, p = 0.008) as well as an increase in the carbonyl levels (p = 0.001) and D3 activity (~33%, p<0.001). Exercise training resulted in a decrease in left ventricular mass, restored cardiac output (~34%, p = 0.048) and ejection fraction (~20%, p = 0.040), increased TRx (~85%, p = 0.007) and reduced carbonyl levels (p<0.001) and D3 activity (p<0.001). CONCLUSIONS: Our short-term exercise training helped reverse the effects of MI on cardiac function. These benefits seem to derive from a more efficient antioxidant response and lower D3 activity in cardiac tissue.

Correlations between Traditional and Nontraditional Indicators of Adiposity, Inflammation, and Monocyte Subtypes in Patients with Stable Coronary Artery Disease.

Background: Recruitment of monocytes and low-grade inflammation process are both involved in obesity and in atherosclerosis. Thus, the aim of this study was to evaluate the correlation among indicators of adiposity, monocyte subtypes, and inflammatory markers in patients with stable coronary artery disease (CAD). Methods: This was a cross-sectional study including 97 patients with stable CAD aged >40 years. Traditional anthropometric indicators of adiposity (body mass index (BMI); waist, hip, and neck circumferences; and waist-hip ratio) and nontraditional anthropometric indicators of adiposity (lipid accumulation product index (LAP), visceral adiposity index (VAI), and deep-abdominal-adipose-tissue index (DAAT)) were determined. Immunoprecipitation, turbidimetry, coagulometric method, and CBA were used for the evaluation of inflammatory markers (hs-CRP, IL-2, IL-4, IL-6, IL-10, and INF-γ). Monocyte subtypes were identified by flow cytometry and defined as CD14++ CD16- (Mon1), CD14++ CD16+ (Mon2), and CD14+ CD16++ (Mon3). Pearson's correlation coefficient and adjusted partial correlation were calculated. Results: Monocyte subtypes were correlated with inflammation regardless of nutritional status according to BMI. In overweight individuals, LAP was correlated with IL-4 and fibrinogen (P < 0.01 and P < 0.05, respectively) and VAI with IL-4 (P < 0.05). In obese patients, the BMI, waist, neck, and hip circumferences, and DAAT were correlated with IL-6 (P < 0.05), regardless of age and sex. The hip circumference was correlated positively with Mon1 (r = 0.40, P = 0.007) and negatively with Mon3 (r = -0.35, P = 0.02) in obese subjects. Conclusion: Monocyte subtypes are correlated with inflammation in patients with stable CAD independently of BMI, whereas traditional and nontraditional indicators of adiposity are correlated differently with inflammatory markers and monocytes, according to the nutritional status.

CRISPR/Cas 9 system for the treatment of dilated cardiomyopathy: A hypothesis related to function of a MAP kinase.

Dilated cardiomyopathy (DCM) is a disease with high incidence and mortality rates. Its therapies have one primary goal, which is to minimize symptoms and it has only one effective approach to healing, the heart transplantation. As it is widely associated with genetic causes, the use of gene therapies, such as the CRISPR/Cas9 system, is a promising alternative to treat DCM. For this purpose, it is necessary to analyze possible target genes for this approach and what would be the implications of their use. Here, we hypothesized that cardiac troponin I type 3 interacting kinase (TNI3K), involved with superoxide production in DCM patients, besides other factors, could be a good target for the use of gene editing.

Leishmanicidal and antichemotactic activities of icetexanes from Salvia uliginosa Benth.

BACKGROUND: Several species of Salvia are used as medicinal plants around the world. Biological activities of isolated compounds have been described, being diterpenes frequently responsible for the effects. PURPOSE: Isolation of diterpenes from Salvia uliginosa Benth. and evaluation of the antichemotactic and leishmanicidal activities of the isolated compounds. STUDY DESIGN: To isolate diterpenes from S. uliginosa and evaluate their antichemotactic and leishmanicidal activities in vitro. METHODS: The exudate of S. uliginosa was obtained by rapidly dipping the aerial parts in dichloromethane. The compounds were isolated by repeated column chromatography over silica gel. The effects on L. amazonensis growth, survival, DNA degradation, ROS generation, as well as the antichemotactic activity and cytotoxicity of the compounds towards human erythrocytes and macrophages were evaluated. RESULTS: A novel icetexane diterpene, isoicetexone (IsoICT) along with the known diterpenes icetexone (ICT), and 7-acetoxy-6,7-dihydroicetexone were isolated from the dichloromethane surface exudate of S. uliginosa. The structures were elucidated using NMR and MS experiments, and by comparison with previously reported data. IsoICT and ICT at low concentrations caused completely inhibition of neutrophils migration in vitro. In addition, IsoICT and ICT showed high leishmanicidal activity against L. amazonensis, induced ROS production in parasites and presented low cytotoxicity against macrophages and human erythrocytes, and moderate to high selectivity index. CONCLUSION: These data indicated that IsoICT and ICT exhibit potent antichemotactic and leishmanicidal effects. Further studies are needed in order to evaluate the in vivo activities as well as the toxicity of the compounds.

Vascular endothelial growth factor association with angiopoietin 1 promotes improvement in ventricular function after ischemic cardiomyopathy induced in mini pigs.

PURPOSE: To investigate the safety and clinical, hemodynamic and tissue improvement ability in mini pigs undergoing cell and gene therapy for the treatment of acute myocardial infarction. METHODS: Thirty-two mini pigs Br1 lineage, 12 months old, undergoing induction of acute myocardial infarction by occlusion of the diagonal branch of the paraconal coronary. They were divided into 4 groups: one control group and 3 treatment groups (cell therapy and gene cell therapy). Echocardiography reviews were performed on three occasions and histopathological analysis was performed after 4 weeks. Analysis of variance (ANOVA), Tukey and Wilcoxon tests, were performed. RESULTS: Association of vascular endothelial growth factor (VEGF) with angiopoietin1 (Ang1) presented satisfactory results in the improvement of ventricular function following ischemic cardiomyopathy in mini pigs when compared to the results of the other treated groups. CONCLUSION: The therapy with VEGF and the combination of VEGF with Ang1, promoted recovered function of the myocardium, characterized by reduced akinetic area and induction of neovascularization.

The homing of bone marrow stem cells is differentially activated in ischemic and valvular heart diseases and influenced by beta-blockers.

BACKGROUND: Cell homing is the mechanism by which an injury releases signaling molecules that cause recruitment, proliferation, migration and differentiation of progenitor cells. Stromal derived factor-1 (SDF-1) and its receptor CXCR4 are key molecules involved in homing and little is known about their activation in cardiopathies. Here, we assessed the homing activation status of bone marrow cells (BMC) concerning the SDF-1 and CXCR4 expression in ischemic (IHD) and valvular (VHD) heart diseases. METHODS: The SDF-1 and inflammatory profile were analyzed by ELISA from plasma obtained bone marrow of ischemic heart patients (IHD, n = 41), valvular heart patients (VHD, n = 30) and healthy controls (C, n = 9). Flow cytometry was used to evaluate CXCR4 (CD184) expression on the surface of bone marrow cells, and the CXCR4 expression was estimated by real-time quantitative PCR. RESULTS: The SDF-1 levels in the groups IHD, VHD and control were, respectively, 230, 530 and 620 pg/mL (P = 0.483), and was decreased in VHD patients using beta-blockers (263 pg/mL) when compared with other (844 pg/mL) (P = 0.023). Compared with IHD, the VHD group showed higher CXCR4 (P = 0.071) and CXCR7 (P = 0.082) mRNA expression although no difference in the level of CXCR4+ bone marrow cells was found between groups (P = 0.360). CONCLUSION: In conclusion, pathophysiological differences between IHD and VHD can affect the molecules involved in the activation of homing. In addition, the use of beta-blockers appears to interfere in this mechanism, a fact that should be considered in protocols that use BMC.

ß-blockers interfere with cell homing receptors and regulatory proteins in a model of spontaneously hypertensive rats.

AIM: To examine the interference of ß-blockers with the chemokine stromal cell-derived factor-1 (SDF-1) found in cell homing receptors, C-X-C chemokine receptor type 4 (CXCR-4) and CXCR-7, and regulatory proteins of homing pathways, we administered atenolol, carvedilol, metoprolol, and propranolol for 30 days using an orogastric tube to hypertensive rats. METHOD: We collected blood samples before and after treatment and quantified the levels of SDF-1 with enzyme-linked immunosorbent assay (ELISA). On day 30 of treatment, the spontaneously hypertensive rats (SHR) were euthanized, and heart, liver, lung, and kidney tissues were biopsied. Proteins were isolated for determining the expression of CXCR-4, CXCR-7, GRK-2 (G protein-coupled receptors kinase 2), ß-arrestins (ß1-AR and ß2-AR), and nuclear factor kappa B (NFκB). RESULTS: We found that the study drugs modulated these proteins, and metoprolol and propranolol strongly affected the expression of ß1-AR (P = .0102) and ß2-AR (P = .0034). CONCLUSION: ß-blockers modulated tissue expression of the proteins and their interactions following 30 days of treatment. It evidences that this class of drugs can interfere with proteins of cell homing pathways.