Acute effect of coffee on arterial stiffness and endothelial function in overweight and obese individuals: A randomized clinical trial.

INTRODUCTION: Coffee is one of the most consumed foodstuffs worldwide. Studies of coffee intake in healthy subjects have shown controversial effects on vascular function. However, little is known of coffee intake effects on the endothelium of overweight and obese individuals. OBJECTIVE: To investigate the acute effects of caffeinated and decaffeinated coffee intake on the endothelial function and arterial stiffness in overweight and obese individuals. METHODS: A randomized, double-blind, crossover clinical trial was designed to investigate the effects of regular caffeinated coffee and decaffeinated coffee on the endothelium. Each subject had both caffeinated coffee and decaffeinated coffee, separated by a washout period of seven days. The endothelial function was measured by flow-mediated dilation (FMD) assessed by ultrasound. Arterial stiffness was measured by an automatic oscillometric device. Blood samples were collected to assess the lipid and nitric oxide profiles. RESULTS: There were 18 subjects included in the study, aged 37.4 ± 10.0 years, with an average BMI of 28.96 ± 2.42, with the majority being female (61.1%). The caffeinated coffee increased central systolic blood pressure (P < 0.001), central diastolic blood pressure (P < 0.001) and pulse wave velocity (P < 0.001), but the decaffeinated coffee did not affect these variables. However, there was a better effect on FMD in the caffeinated coffee intake group (P = 0.014). CONCLUSION: In overweight and obese individuals, caffeinated coffee increased central blood pressure and pulse wave velocity but not the decaffeinated coffee. While caffeinated coffee showed an improvement on hyperemia-induced endothelial function. REGISTRATION NUMBER OF CLINICAL TRIAL: Platform of the Brazilian Registry of Clinical Trials under number RBR-65cxtr.

Antiplatelet Activity of Isorhamnetin via Mitochondrial Regulation.

With the diet, we ingest nutrients capable of modulating platelet function, which plays a crucial role in developing cardiovascular events, one of the leading causes of mortality worldwide. Studies that demonstrate the antiplatelet and antithrombotic potential of bioactive compounds are vital to maintaining good cardiovascular health. In this work, we evaluate the flavonol isorhamnetin's antiplatelet effect on human platelets, using collagen, thrombin receptor activator peptide 6 (TRAP-6), and phorbol myristate acetate (PMA) as agonists. Isorhamnetin induced a significant inhibition on collagen- and TRAP-6-induced platelet aggregation, with half-maximum inhibitory concentration (IC50) values of 8.1 ± 2.6 and 16.1 ± 11.1 µM, respectively; while it did not show cytotoxic effect. Isorhamnetin reduced adenosine triphosphate levels (ATP) in platelets stimulated by collagen and TRAP-6. We also evidenced that isorhamnetin's antiplatelet activity was related to the inhibition of mitochondrial function without effect on reactive oxygen species (ROS) levels. Additionally, we investigated isorhamnetin's effect on thrombus formation in vitro under flow conditions on the damaged vessel wall. In this context, we demonstrate that isorhamnetin at 20 µM induced a significant inhibition on platelet deposition, confirming its antithrombotic effect. Our findings corroborate the antiplatelet and antithrombotic potential of isorhamnetin present in many foods of daily consumption.

Frail older adults show a distinct plasma microvesicle profile suggesting a prothrombotic and proinflammatory phenotype.

In a global context of advanced aging, geriatric diseases such as frailty syndrome face challenges in the search for biomarkers and preventive strategies. Frailty has been associated with atherothrombotic pathologies. Circulating microvesicles (cMVs), phospholipid-rich vesicles with a size of 0.1-1.0 µm, have been shown to participate in atherothrombosis onset and progression. We have hypothesized that cMVs from platelets, and vascular and immune cells, are increased in frail older adults. To verify this, a prevalent-case control study was designed with 28 frail older and 27 nonfrail older adults older than 64 years. Frailty was defined by Fried's phenotype. Total cMVs, annexin V positive (AV+)-cMVs, and annexin V negative (AV- )-cMVs derived from blood and vascular cells were measured by flow cytometry. In the analysis of total cMVs, the frail group presented higher levels of CD14+ /CD142+ (p = .042), CD41a+ /CD142+ (p = .041), and CD56+ (p = .025), CD14+ cMVs (p = .043), and CD16+ /CD14+ (p = .019) cMVs levels. Within the phosphatidylserine-exposing cMVs (AV+ ), the frail group showed higher CD14+ /AV+ (p = .044), CD9+ /AV+ (p = .031), P2RY12+ /AV+ (p = .028), and CD235a+ /AV+ (p = .043) cMVs concentrations. Finally, within AV- cMVs, the frail group showed higher CD142+ /CD41a+ /AV- cMVs concentrations originated from platelets (p = .027), CD56+ /AV- originated from natural killer cells (p = .022), and CD34+ /AV- cMVs from hematopoietic stem cells (p = .037). In summary, frail older adults present higher concentrations of platelet-, leukocyte-, and hematopoietic cell-derived cMVs compared to robust age-matched older adults. These cMVs may be involved in the deregulation of the immune system, endothelial damage, and increased risk of thrombosis associated with frailty.

Guanosine exerts antiplatelet and antithrombotic properties through an adenosine-related cAMP-PKA signaling.

BACKGROUND: Guanosine is a natural product and an endogenous nucleoside that has shown to increase during myocardial ischemia. Platelets are critically involved in ischemic coronary events. It remains unknown, however, whether guanosine may affect platelet activation and function. We sought to investigate the potential antiplatelet and antithrombotic properties of guanosine and decipher the mechanisms behind. METHODS: We firstly assessed the effects of guanosine on platelet activation/aggregation upon stimulation with several platelet agonists including adenosine diphosphate (ADP), collagen, arachidonic acid (AA), and TRAP-6. Guanosine antithrombotic potential was also evaluated both in vitro (Badimon perfusion chamber) and in vivo (murine model). In addition we assessed any potential effect on bleeding. At a mechanistic level we determined the release of thromboxane B2, intraplatelet cAMP levels, the binding affinity on platelet membrane, and the activation/phosphorylation of protein kinase A (PKA), phospholipase C (PLC) and PKC. RESULTS: Guanosine markedly inhibited platelet activation/aggregation-challenged by ADP and, although to a lesser extent, also reduced platelet aggregation challenged by collagen, AA and TRAP-6. Guanosine significantly reduced thrombus formation both in vitro and in vivo without significantly affects bleeding. Guanosine antiplatelet effects were associated with the activation of the cAMP/PKA signaling pathway, and a reduction in thromboxane B2 levels and PLC and PKC phosphorylation. The platelet aggregation and binding affinity assays revealed that guanosine effects on platelets were mediated by adenosine. CONCLUSION: Guanosine effectively reduces ADP-induced platelet aggregation and limits thrombotic risk. These antithrombotic properties are associated with the activation of the cAMP/PKA signaling pathway.

Association of alcohol consumption with coronary artery disease severity.

BACKGROUND & AIMS: The ingestion of small to moderate alcohol consumption amounts has been associated to cardiovascular protection. This study aimed to evaluate the association between alcohol consumption and coronary artery disease severity. MATERIAL AND METHODS: Cross-sectional Study with patients undergoing coronary angiography. Age, cardiovascular risk factors (smoking, systemic arterial hypertension, dyslipidemia and diabetes) and alcohol drinking habit were investigated. Alcohol consumption was divided in three categories: nondrinker, moderate alcohol consumption (less than 15 g ethanol/day for women or 30 g ethanol/day for men) and heavy alcohol consumption. Coronary artery disease severity was assessed through the Friesinger Score (FS) in the coronary angiography, by interventional cardiologists blinded to alcohol consumption. RESULTS: The final sample included 363 adults; of those, 228 were men (62.81%). Mean age was 60.5 ± 10.9 y. Unadjusted analyses identified sex, age, hypertension, diabetes, dyslipidemia and alcohol consumption as the main covariates associated with the Friesinger score. Lower Friesinger scores were also observed in moderate alcohol consumption when comparing to those who do not drink (RR 0.86; 95% CI 0.79-0.95). CONCLUSION: Among patients with suspected coronary artery disease undergoing coronary angiography, moderate alcohol consumption is associated to a lower coronary artery disease severity than heavy drinking.

Mechanisms of chronic state of inflammation as mediators that link obese adipose tissue and metabolic syndrome.

The metabolic syndrome is a cluster of cardiometabolic alterations that include the presence of arterial hypertension, insulin resistance, dyslipidemia, and abdominal obesity. Obesity is associated with a chronic inflammatory response, characterized by abnormal adipokine production, and the activation of proinflammatory signalling pathways resulting in the induction of several biological markers of inflammation. Macrophage and lymphocyte infiltration in adipose tissue may contribute to the pathogenesis of obesity-mediated metabolic disorders. Adiponectin can either act directly on macrophages to shift polarization and/or prime human monocytes into alternative M2-macrophages with anti-inflammatory properties. Meanwhile, the chronic inflammation in adipose tissue is regulated by a series of transcription factors, mainly PPARs and C/EBPs, that in conjunction regulate the expression of hundreds of proteins that participate in the metabolism and storage of lipids and, as such, the secretion by adipocytes. Therefore, the management of the metabolic syndrome requires the development of new therapeutic strategies aimed to alter the main genetic pathways involved in the regulation of adipose tissue metabolism.

El consumo de futas y hortalizas ayuda a prevenir el daño endotelial / Consumption of fruits and vegetables in the prevention of endothelial damage

The endothelium helps to maintain the normal structure and homeostasis of the vasculature. However, chronic exposure to cardiovascular (CV) risk factors causes endothelial dysfunction, a phenomenon that is characterized by inflammation, reduced bioavailability of nitric oxide (NO) and a prothrombotic state. Epidemiological studies have shown that regular consumption of fruits and vegetables reduces CV risk, which has caused interest in knowing the bioactive compounds and the mechanisms involved. Among the components that protect the endothelium are antioxidants (vitamin C, vitamin E and poly phenols) and polyunsaturated fatty acids. Vitamin C and E promote vasodilatation protecting NO by blocking the reactive oxygen species (ROS). Poly phenols improve endothelial function primarily by increasing levels of NO, and inhibition of angiogenesis and platelet activation. Diets rich in poly-unsaturated fatty acids have shown beneficial effects by reducing the gene expression of cyclooxygenase-2 and the expression of cell adhesion molecules. This review mainly highlights the current understanding of endothelial dysfunction and the protective effect of endothelial cells by bioactive components of fruits and vegetables.

El endotelio normal ayuda a mantener la estructura y la hemostasia vascular. Sin embargo, la exposición crónica a factores de riesgo cardiovascular (CV) produce disfunción endotelial, fenómeno que se caracteriza por inflamación, disminución en la biodisponibilidad de óxido nítrico (NO) y un estado protrombótico. Estudios epidemiológicos han demostrado que el consumo regular de frutas y hortalizas disminuye el riesgo CV, lo que ha causado interés en conocer los compuestos bioactivos y los mecanismos involucrados. Entre los componentes que protegen el endotelio se encuentran las moléculas antioxidantes (vitamina C, vitamina E y polifenoles) y ácidos grasos poliinsaturados. Las vitaminas C y E favorecen la vasodilatación protegiendo el NO al bloquear las especies reactivas del oxigeno (ROS). Los polifenoles mejoran la función endotelial principalmente por el aumento de los niveles de NO, y la inhibición de la angiogénesis y de la activación plaquetaria. Dietas ricas en ácidos grasos poliinsaturados han mostrado efectos beneficiosos, mediante la reducción de la expresión géni-ca de la ciclooxigenasa-2 y de la expresión de moléculas de adhesión celular. Esta revisión principalmente señala los conocimientos actuales de la disfunción endotelial y el efecto protector de las células endoteliales por componentes bioactivos de frutas y hortalizas.

Simultaneous inhibition of TXA(2) and PGI(2) synthesis increases NO release in mesenteric resistance arteries from cirrhotic rats.

Our present study examines, in mesenteric resistance arteries, possible vasodilation alterations, and the role of NO and COX (cyclo-oxygenase) derivatives, in cirrhosis. The vasodilator response to acetylcholine was analysed in segments from control and cirrhotic rats. The effects of the non-specific COX inhibitor indomethacin, the specific COX-1 inhibitor SC-560 and the specific COX-2 inhibitor NS-398 were analysed in segments from both groups of rats. NO release was measured, and eNOS [endothelial NOS (NO synthase)], phospho-eNOS, iNOS (inducible NOS), COX-1 and COX-2 protein expression was also analysed. The effects of the TP receptor [TXA2 (thromboxane A(2)) receptor] antagonist SQ 29548, the TXA(2) synthesis inhibitor furegrelate, the PGI(2) (prostaglandin I(2)) synthesis inhibitor TCP (tranylcypromine) or TCP+furegrelate were only determined in segments from cirrhotic rats. The vasodilator response to acetylcholine was higher in segments from cirrhotic rats. Indomethacin, SC-560 and NS-398 did not modify the vasodilator response in control rats; however, indomethacin, NS-398 and TCP+furegrelate increased, whereas SC-560 did not modify and SQ 29548, furegrelate or TCP decreased, the vasodilator response to acetylcholine in cirrhotic rats. NO release was higher in cirrhotic rats. Furegrelate decreased, whereas TCP+furegrelate increased, the NO release in segments from cirrhotic rats. eNOS and COX-1 protein expression was not modified, whereas phosho-eNOS, iNOS and COX-2 protein expression was higher in cirrhotic rats. Therefore the increase in iNOS expression and eNOS activity may mediate increases in endothelial NO release. The COX-2 derivatives TXA(2) and PGI(2) may act simultaneously, producing a compensatory effect that reduces NO release and may limit the hyperdynamic circulation.