α acid fraction from Hop extract exerts an endothelium-derived hyperpolarization vasorelaxant effect through TRPV4 employing the feedforward mechanism of PKCα.

Until now, the beneficial vascular properties of Hop reported in the literature have been mainly attributed to specific compound classes, such as tannins and phenolic acids. However, the potential vascular action of a Hop subfraction containing a high amount of α or ß acids remains completely understood. Therefore, this study aims to investigate the vascular effects of the entire Hop extract and to fraction the Hop extract to identify the main bioactive vascular compounds. A pressure myograph was used to perform vascular reactivity studies on mouse resistance arteries. Phytocomplex fractionation was performed on a semi-prep HPLC system and characterized by UHPLC-PDA-MS/MS coupled to mass spectrometry. Western blot analysis was performed to characterize the phosphorylation site enrolled. The entire Hop extract exerts a direct dose-dependent endothelial vascular action. The B1 subfraction, containing a high concentration of α acids, recapitulates the vascular effect of the crude extract. Its vasorelaxant action is mediated by the opening of Transient Receptor Potential Vanilloid type 4 (TRPV4), potentiated by PKCα, and subsequent involvement of endothelial small-conductance calcium-activated potassium channels (SKCa) and intermediate-conductance calcium-activated potassium channels (IKCa) that drives endothelium-dependent hyperpolarization (EDH) through heterocellular myoendothelial gap junctions (MEGJs). This is the first comprehensive investigation of the vascular function of Hop-derived α acids in resistance arteries. Overall, our data suggest that the B1 subfraction from Hop extracts, containing only α acids, has great potential to be translated into the useful armamentarium of natural bioactive compounds with cardiovascular benefits.

Beneficial Effects of Spirulina Supplementation in the Management of Cardiovascular Diseases.

In recent decades, as a result of rising mortality rates due to cardiovascular diseases (CVDs), there has been a growing urgency to find alternative approaches to conventional pharmaceutical treatment to prevent the onset of chronic diseases. Arthrospira platensis, commonly known as Spirulina, is a blue-green cyanobacterium, classified as a "superfood", used worldwide as a nutraceutical food supplement due to its remarkable nutritional value, lack of toxicity, and therapeutic effects. Several scientific studies have evaluated the cardioprotective role of Spirulina. This article presents a comprehensive review of the therapeutic benefits of Spirulina in improving cardio- and cerebrovascular health. It focuses on the latest experimental and clinical findings to evaluate its antihypertensive, antidiabetic, and antihyperlipidemic properties. The objective is to highlight its potential in preventing and managing risk factors associated with cardiovascular disease (CVD).

C2CD4B Evokes Oxidative Stress and Vascular Dysfunction via a PI3K/Akt/PKCα-Signaling Pathway.

High glucose-induced endothelial dysfunction is an important pathological feature of diabetic vasculopathy. While genome-wide studies have identified an association between type 2 diabetes mellitus (T2DM) and increased expression of a C2 calcium-dependent domain containing 4B (C2CD4B), no study has yet explored the possible direct effect of C2CD4B on vascular function. Vascular reactivity studies were conducted using a pressure myograph, and nitric oxide and oxidative stress were assessed through difluorofluorescein diacetate and dihydroethidium, respectively. We demonstrate that high glucose upregulated both mRNA and protein expression of C2CD4B in mice mesenteric arteries in a time-dependent manner. Notably, the inhibition of C2CD4B expression by genetic knockdown efficiently prevented hyperglycemia-induced oxidative stress, endothelial dysfunction, and loss of nitric oxide (NO) bioavailability. Recombinant C2CD4B evoked endothelial dysfunction of mice mesenteric arteries, an effect associated with increased reactive oxygen species (ROS) and decreased NO production. In isolated human umbilical vein endothelial cells (HUVECs), C2CD4B increased phosphorylation of endothelial nitric oxide synthase (eNOS) at the inhibitory site Thr495 and reduced eNOS dimerization. Pharmacological inhibitors of phosphoinositide 3-kinase (PI3K), Akt, and PKCα effectively attenuated oxidative stress, NO reduction, impairment of endothelial function, and eNOS uncoupling induced by C2CD4B. These data demonstrate, for the first time, that C2CD4B exerts a direct effect on vascular endothelium via a phosphoinositide 3-kinase (PI3K)/Akt/PKCα-signaling pathway, providing a new perspective on C2CD4B as a promising therapeutic target for the prevention of oxidative stress in diabetes-induced endothelial dysfunction.

Platelet­to­lymphocyte ratio, neutrophil­to­lymphocyte ratio and monocyte­to­HDL cholesterol ratio as helpful biomarkers for patients hospitalized for deep vein thrombosis.

There is an increased interest for novel biomarkers in order to improve the diagnostic accuracy for deep vein thrombosis (DVT). Moreover, the link between inflammation and venous thromboembolism has attracted increasing research interests. The present study aimed to evaluate the role of the platelet­to­lymphocyte ratio (PLR), neutrophil­to­lymphocyte ratio (NLR) and monocyte­to­high­density lipoprotein cholesterol ratio (MHR) as biomarkers for acute DVT. For this purpose, 300 consecutive patients who were hospitalized were considered; 33 patients out of the 300 were admitted for acute DVT of the lower limbs. The PLR, NLR and MHR, as well as the acute phase inflammation markers (leukocytes, neutrophils, C­reactive protein and fibrinogen) were measured. The patients with DVT exhibited significantly higher levels of PLR, NLR and MHR compared to those without DVT (P<0.001). Simple binary linear regression analysis (without confounding factors) between the NLR, PLR and MHR highest quartile and DVT revealed an odds ratio of 3.149 (P=0.01) for PLR, and an odds ratio of 4.191 (P=0.001) for MHR. Following the correction for the main confounding factors, PLR maintained a significant association with DVT (odds ratio, 3.379; P=0.007) and MHR maintained a stronger significant association with DVT (odds ratio, 4.378; P=0.001). It was thus hypothesized that the assessment of PLR and MHR, but not of NLR may help clinicians to improve the laboratory evaluation in elderly hospitalized patients with suspected DVT.

The Dark Side of Sphingolipids: Searching for Potential Cardiovascular Biomarkers.

Cardiovascular diseases (CVDs) are the leading cause of death and illness in Europe and worldwide, responsible for a staggering 47% of deaths in Europe. Over the past few years, there has been increasing evidence pointing to bioactive sphingolipids as drivers of CVDs. Among them, most studies place emphasis on the cardiovascular effect of ceramides and sphingosine-1-phosphate (S1P), reporting correlation between their aberrant expression and CVD risk factors. In experimental in vivo models, pharmacological inhibition of de novo ceramide synthesis averts the development of diabetes, atherosclerosis, hypertension and heart failure. In humans, levels of circulating sphingolipids have been suggested as prognostic indicators for a broad spectrum of diseases. This article provides a comprehensive review of sphingolipids' contribution to cardiovascular, cerebrovascular and metabolic diseases, focusing on the latest experimental and clinical findings. Cumulatively, these studies indicate that monitoring sphingolipid level alterations could allow for better assessment of cardiovascular disease progression and/or severity, and also suggest them as a potential target for future therapeutic intervention. Some approaches may include the down-regulation of specific sphingolipid species levels in the circulation, by inhibiting critical enzymes that catalyze ceramide metabolism, such as ceramidases, sphingomyelinases and sphingosine kinases. Therefore, manipulation of the sphingolipid pathway may be a promising strategy for the treatment of cardio- and cerebrovascular diseases.

Platelet­to­lymphocyte ratio, neutrophil­to­lymphocyte ratio and monocyte­to­HDL cholesterol ratio as markers of peripheral artery disease in elderly patients.

Solid evidence underlines the pivotal role played by inflammation regarding atherosclerosis. Peripheral artery disease (PAD) is one of atherosclerotic cardiovascular diseases (CVDs), it is highly frequently diagnosed in older individuals. In the present study we carried out an investigation on the association between platelet­to­lymphocytes ratio (PLR), neutrophil­to­lymphocyte ratio (NLR), monocyte­to­HDL cholesterol ratio (MHR) with PAD as favourable markers. We identified 300 subjects aged over 70 years, without any concomitant CVDs. The PLR, NLR and MHR were assessed from peripheral venous blood routinely drawn in the ward during hospitalization. Patients were divided in groups according to ankle brachial index (ABI) value (>0.9; 0.9­0.99; 1­1.4; >1.4). Higher PLR (P=0.007), NLR (P=0.0001) and MHR (P=0.0001) were associated with <0.9 ABI. Patients with a >1.4 ABI showed NLR values higher compared to >0.9l ABI (P<0.01). Univariate linear regression analysis demonstrated the direct correlation between increase in PLR (P=0.0023)and MHR (P<0.0001) with the decrease in ABI value. In multivariate linear regression analysis including main cardiovascular risk factors we found that PLR, NLR and MHR were independently associated with lower ABI (P=0.0011). Results show and suggest that the elevated PLR, NLR and MHR are related to PAD evaluated with ABI measurement. PLR and MHR seem to be more reliable markers than NLR in PAD. NLR seems to be more related to incompressibility of arterial wall. It is hypothesized that these three indexes may play a role as simple and repetitive markers of PAD.