Cardiovascular & Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Cardiovascular & Hematological Agents) - Volume 16, Issue 2, 2018

Background: Lipid-lowering therapy and control of cardiovascular risk factors are the current recommendations of atherosclerotic disease management. Despite optimal treatment the rate of acute coronary syndrome events remains high. Inflammation plays an essential role in the pathophysiology of atherosclerotic plaque formation, progression and rupture, which conclusively causes acute clinical episodes. Objective: This review aims to give a conceptual description of the potential therapeutic benefits and effects of colchicine in inflammation-mediated atherosclerotic disease and hypertriglyceridemia. Method: A complete literature survey was performed using the PubMed database search to collect available information regarding colchicine, atherosclerosis, and hypertriglyceridemia. Results: A total of 42 studies met the selection criteria for inclusion in the review. Inflammation is a well-known key mediator of atherogenesis in coronary artery disease. Colchicine has direct antiinflammatory effects by inhibiting critical inflammatory signaling networks as the inflammasome, pro-inflammatory cytokines, and expression of adhesion molecules, preventing both local chemoattraction of inflammatory cells such as neutrophils and systemic inflammation including the decrease of the release of IL-1β by the neutrophils. Conclusion: Colchicine reduces the levels of inflammatory markers, stabilizes the coronary plaque, leads to more favorable cardiac healing after damage, and reduces the acute coronary syndromes event recurrence. Colchicine reduces the myocardial infarct size, myocardial fibrosis, and improves the hemodynamic parameters. Several studies report the potential attenuating role of colchicine on triglyceride levels. Current evidence though regarding the pathophysiological mechanism of colchicine’s triglyceride-lowering effect remains scarce.

Atherothrombosis-related diseases are one of the world’s leading causes of mortality, and thus the search for new therapeutic approaches in this area remains a very urgent task. Modern pharmacogenomic technologies make it possible to obtain valuable data on disease pathogenesis and optimal therapeutic approaches. One promising research direction is the study of the thromboxane A2 - thromboxane A synthase - thromboxane A2 receptor axis. This review summarizes the recent evidence and suggests that systematic works in this area are creating new and promising opportunities in the treatment of patients with cardiovascular diseases.

Idiopathic Edema (IE), is a syndrome involving real or perceived weight gain secondary to the pathological retention of fluid. This syndrome of generalized edema is almost solely reported in women. The diagnosis of IE is one of exclusion and requires a careful history, physical exam, and clinical suspicion. The aim of this article is to provide a comprehensive review of the available literature in order to attempt to define IE, identify the possible causes, review the proposed pathophysiology, and discuss potential treatment options.

Objective: The present study was carried out in order to evaluate the antidiabetic and antihyperlipidemic potential of Flavonoid-Rich Extract of Tamarix articulata (FRETA) in both normal and Streptozotocin (STZ)-induced diabetic rats. Material and Methods: Normal and diabetic rats were treated with the FRETA for 7 days. At the end of treatment, a range of parameters was tested including blood lipid profile, histopathological changes in both liver and pancreas and Oral Glucose Tolerance Test (OGTT). Results: The blood glucose levels were lowered in both normal and diabetic rats treated with FRETA. Single oral administration of FRETA reduced blood glucose levels significantly in both normal and diabetic rats six hours after administration (P < 0.001; P < 0.0001 respectively). Furthermore, blood glucose levels were decreased significantly (P < 0.0001) in diabetic rats after 7 days of treatment. According to the oral glucose tolerance test, FRETA (5 mg/kg) was shown to prevent significantly the increase in blood glucose levels in diabetic treated rats. In addition, FRETA (5 mg/kg) showed a strong hypolipidemic effect both in normal and STZ rats after 7 days of once daily oral treatment. FRETA induced a significant decrease of plasma triglyceride and total cholesterol concentrations both in normal and diabetic rats. In contrast, plasma HDL-c levels were increased significantly (P < 0.0001) both in normal and diabetic rats. In addition, FRETA showed a remarkable in vitro antioxidant activity and revealed the inhibitory concentration of 50% of free radicals (IC50) of 31.92 μg/ml. Conclusion: In diabetic rats, flavonoids from Tamarix articulata showed antidiabetic and hypolipidemic activities.

Background: Achieving a good satisfaction with anticoagulant treatment should be a target in Atrial Fibrillation (AF) patients. Objective: To ascertain the perception of patients regarding burdens and benefits of anticoagulation with Vitamin K Antagonists (VKA). Methods: This was a multicenter cross-sectional/retrospective study conducted throughout Spain, in which AF patients taking VKA during the last year, attended at primary care setting were included. The Anti-Clot-Treatment Scale (ACTS) was used to determine perceived burdens and benefits with anticoagulation. Results: Overall, 1,386 patients (mean age 77.4 ± 8.7 years; 48.6% women; 64.2% permanent AF; CHA2DS2-VASc 3.9 ± 1.5; HAS-BLED 1.6 ± 0.9) were analyzed. The adequate anticoagulation control was achieved by 56.9/60.6% of patients according to direct method/Rosendaal method, respectively. Overall, mean ACTS Burdens scale score was 49.4 ± 8.8 and mean ACTS Benefits scale score 11.2 ± 2.2. Active patients, polymedication, elderly and visits to the nurse were associated with higher scores in the ACTS Burdens scale (lower perceived burden), whereas visits to the emergency department and primary care physician were associated with lower scores in the ACTS Burdens scale (higher perceived burden). Active patients, number of INR determinations, visits to the nurse, and an adequate INR control were associated with higher scores in the ACTS Benefits scale (higher perceived benefit), whereas visits to the emergency department and to the primary care physician were associated with lower scores in the ACTS Benefits scale (lower perceived benefit). Conclusion: Satisfaction with treatment was high among patients with AF chronically anticoagulated with VKA, suggesting that quality of life is not impaired in this population.

Background: Atherosclerosis is a chronic inflammatory disease which may lead to major cardiovascular events. The primary cause of atherosclerosis is Dyslipidemia. The increased level of lipid profile triggers endothelial dysfunction. This results in inflammation with the recruitment of monocyte, macrophage, T lymphocyte, and Mast cells secreted by an Lp-PLA2 enzyme which causes binding between macrophage and oxidized LDL. This binding results in the formation of foam cells and also the migration of smooth muscle cells. Following that, an Lp-PLA2 receptor hydrolizes OxPC which results in LysoPC and OxNEFA, bioactive compounds which stimulate the progression of atherosclerosis plaques. This process leads to cell hypoxia, which may result in the increase of HIF-1α and VEGF expressions and induction of vasa vasorum angiogenesis. Employing darapladib as an agent of Lp-PLA2 selective inhibitors, this study aimed to find out the effect of darapladib as an Lp- PLA2 selective inhibitor agent on the formation of vasa vasorum angiogenesis and the decrease of HIF-1α and VEGF expression in aortic tissue of rats with dyslipidemia. Method: A true laboratory experiment with a randomized post-test control group design used 30 male spraque dowley rats as animal models which were divided into 6 groups: Normal 8 weeks, Normal 16 weeks, Dyslipidemia (DL) 8 weeks, Dyslipidemia (DL) 16 weeks, Dyslipidemia with darapladib treatment (DLDP) 8 weeks and Dyslipidemia with darapladib treatment (DLDP) 16 weeks. The data measured in this study were the lipid profile (total cholesterol, HDL, and LDL). Using EnzyChrom TM kit, hematoxylin eosin, and double-labelling immunofluorescene, the levels of lipid profile, vasa vasorum, HIF-1α and VEGF were measured. Results: The study results which were analyzed using NOVA test showed that with darapladib administration, there was a significant decrease in vasa vasorum angiogenesis (p=0.000), HIF-1α (p=0.005) and VEGF (p=0.009) expression in each time series. This result proves that Lp-PLA2 inhibitor reduces inflammatory process. Conclusion: Darapladib injection as an Lp-PLA2 selective inhibitor correlates with the decreasing vasa vasorum angiogenesis through alteration in HIF-1α and VEGF expressions in the aorta of high fat diet rats. We recommend further experiments to determine the effectiveness of darapladib with earlier time series in the atherosclerosis process.

Background: Non-Steroidal Anti Inflammation Drugs (NSAIDs) have shown effectivity in pain relief and are the most prescribed around the world. However, NSAIDs impair hematological aspects that may lead to the life-threatening events. Objective: The objective of the study is to determine the comparison and impact of the short-term use of some non-aspirin NSAIDs on bleeding time. Method: We have 10 animals group. Each group contains 4 animals. Normal group, ketoprofen (0.26 mg/ 20 g BW of mice twice daily), ketorolac (0.078 mg/ 20 g BW of mice twice daily), diclofenac (0.13 mg/ 20 g BW of mice twice daily), piroxicam (0.052 mg/ 20 g BW of mice once daily), mefenamic acid (1.3 mg/ 20 g BW of mice thrice daily), meloxicam (0.039 mg/ 20 g BW of mice once daily), celecoxib (0.52 mg/ 20 g BW of mice once daily), ibuprofen (1.04 mg/ 20 g BW of mice thrice daily) and paracetamol group (1.3 mg/ 20 g BW of mice thrice daily). The treatment length is 5 days. Bleeding time determination was conducted one hour after the last treatment. Results: All test group showed an elevation of the bleeding time by 59.78%, 156.50%, 108.73%, 99.96%, 22.59%, 85.46%, 69.66%, 42.24%, and 45.08% for meloxicam, ketoprofen, ketorolac, diclofenac sodium, paracetamol, piroxicam, mefenamic acid, ibuprofen and celecoxib than normal groups, respectively. Ketoprofen gives the highest bleeding time elevation. Conclusion: Ketoprofen gives the highest bleeding time elevation while paracetamol gives the lowest bleeding time elevation.