Antithrombotic Factors Research Articles

Evaluation of Long-term Antithrombotic Management for Atrial Fibrillation Patients with a History of Coronary Stent Implantation

Purpose: American expert consensus publications recommend discontinuation of antiplatelet agents 6 to 12 months after Percutaneous Coronary Intervention (PCI) in patients with Atrial Fibrillation (AF) who require chronic anticoagulation, and use of oral anticoagulant monotherapy thereafter. This study aimed to assess real-world long-term antithrombotic therapy management practices and factors associated with the continuation of antiplatelet agents past 12 months post-PCI in patients with AF requiring chronic anticoagulation. Methods: Patients with AF and a history of PCI greater than 12 months before their most recent encounter with physicians at an outpatient electrophysiology clinic were identified by chart review. Patient demographics, clinical characteristics, and current antithrombotic regimen were collected from encounters that occurred between July 2019 and June 2022. The independent predictive factors associated with the continuation of antiplatelet agents were identified using univariate and regression analyses. Results: Out of 66 patients, 67% continued antiplatelet therapy for greater than 12 months post-PCI. Patients on antiplatelets were significantly less likely to have bare metal stents (p = 0.006), be greater than five years post-PCI (p = 0.002), and have a HASBLED score of two or less (p = 0.028) when compared to patients on oral anticoagulant monotherapy. Bare metal stent history (p = 0.045) and HASBLED score of two or less (p = 0.016) were also significant in regression analysis. Conclusion: This study found that most patients with AF and a history of PCI continued antiplatelet therapy longer than 12 months post-PCI, often despite the high bleeding risk.

Innovative Substrate Design with Basement Membrane Components for Enhanced Endothelial Cell Function and Endothelization.

Enhancing endothelial cell growth on small-diameter vascular grafts produced from decellularized tissues or synthetic substrates is pivotal for preventing thrombosis. While optimized decellularization protocols can preserve the structure and many components of the extracellular matrix (ECM), the process can still lead to the loss of crucial basement membrane proteins, such as laminin, collagen IV, and perlecan, which are pivotal for endothelial cell adherence and functional growth. This loss can result in poor endothelialization and endothelial cell activation causing thrombosis and intimal hyperplasia. To address this, the basement membrane's ECM is emulated on fiber substrates, providing a more physiological environment for endothelial cells. Thus, fibroblasts are cultured on fiber substrates to produce an ECM membrane substrate (EMMS) with basement membrane proteins. The EMMS then underwent antigen removal (AR) treatment to eliminate antigens from the membrane while preserving essential proteins and producing an AR-treated membrane substrate (AMS). Subsequently, human endothelial cells cultured on the AMS exhibited superior proliferation, nitric oxide production, and increased expression of endothelial markers of quiescence/homeostasis, along with autophagy and antithrombotic factors, compared to those on the decellularized aortic tissue. This strategy showed the potential of pre-endowing fiber substrates with a basement membrane to enable better endothelization.

Assessing Mailuoning injection in wound healing and thrombophlebitis management: A rat model study.

Thrombophlebitis is the inflammatory condition characterized by obstruction of one or more vessels, commonly in the legs, due to the formation of blood clots. It has been reported that traditional Chinese medicine, including Mailuoning injection, is advantageous for treating inflammatory and blood disorders. This research assessed the therapeutic efficacy of Mailuoning injection in the treatment of thrombophlebitis in rodents, as well as investigated its impact on fibrinolysis, inflammation, and coagulation. An experimental setup for thrombophlebitis was established in rodents via modified ligation technique. Five groups comprised the animals: sham operation group, model group, and three Mailuoning treatment groups (low, medium, and high dosages). The pain response, edema, coagulation parameters (PT, APTT, TT, FIB), serum inflammatory markers (IL-6, TNF-α, CRP), and expression levels of endothelial markers (ICAM-1, VCAM-1, NF-κB) were evaluated. Blood flow and vascular function were further assessed by measuring hemorheological parameters and the concentrations of TXB2, ET, and 6-k-PGF1α. In contrast to the sham group, model group demonstrated statistically significant increases in endothelial expression levels, coagulation latencies, and inflammatory markers (p < 0.05). The administration of mailing, specifically at high and medium dosages, resulted in a substantial reduction in inflammatory markers, enhancement of coagulation parameters, suppression of ICAM-1 and VCAM-1 expression, and restoration of hemorheological measurements to baseline (p < 0.05). Significantly higher concentrations of 6-k-PGF1α and lower levels of TXB2 and ET were observed in high-dose group, suggesting that pro- and anti-thrombotic factors were restored to equilibrium. Utilization of Mailuoning injection in rat model of thrombophlebitis exhibited significant therapeutic impact. This effect was manifested through pain alleviation, diminished inflammation, enhanced blood viscosity and facilitation of fibrinolysis. The study indicated that Mailuoning injection may serve as a viable therapeutic option for thrombophlebitis, potentially aiding in the improvement of wound healing by virtue of its anti-inflammatory and blood flow-enhancing characteristics.

Thrombodynamics and Quantitative phase imaging of platelets in the assessment of hemostasis in pregnant women with protein C / protein S deficiency

Relevance. A hypercoagulable state caused by hereditary or acquired deficiency of antithrombotic factors can contribute to disruption of the uteroplacental circulation with the development of serious pregnancy complications, which requires effective monitoring of hemostasis during the use of pathogenetic anticoagulant therapy.The purpose of the study is to improve methods for diagnosing and monitoring hemostatic disorders in pregnant women with thrombophilia (protein C/protein S deficiency) and complicated pregnancy based on the use of an integral thrombodynamic test and quantitative phase imaging of platelets.Material and methods. 45 pregnant women were examined in the first and second trimester: 20 women with normal pregnancy (comparison group) and 25 (main group) with thrombophilia (protein S/protein C deficiency). 16 pregnant women (subgroup 1A) received a full course of preconception preparation with the prescription of LMWH, 9 pregnant women (subgroup 1B) did not complete the course in full for various reasons. To study hemostasis, along with routine methods (determination of APTT, TT, PT, Fibrinogen, INR and D-dimer), an integral assessment of coagulation using the Thrombodynamics method and quantitative phase imaging (QPI) of platelets in real time were performed.Results. It was found that routine methods are not sufficiently informative; statistically significant changes against the background of thrombophilia and during treatment with LMWH were noted only based on the results of assessing the level of fibrinogen and D-dimer. In the complex of thrombodynamics indicators, the most sensitive parameters were the steady-state clot growth rate (Vst), clot size at 30 minutes of the study (CS) and clot density (D). The QPI method revealed features of the morphological structure of platelets with a predominance in pregnant women with protein S/protein C deficiency of the activated cell population with an increase in the median values of diameter and perimeter by 14 and 20 %, respectively (p &lt; 0.05). The effectiveness of LMWH therapy was assessed by normalization of the analyzed parameters.Conclusion. Timely and adequate correction of hemostasis disorders, carried out while monitoring coagulation and platelet parameters, taking into account all clinical data, can significantly reduce the risk of complications for the mother and fetus.

Endotheliopathy of liver sinusoidal endothelial cells in liver disease.

Liver is the largest solid organ in the abdominal cavity, with sinusoid occupying about half of its volume. Under liver disease, hemodynamics in the liver tissue dynamically change, resulting in injury to liver sinusoidal endothelial cells (LSECs). We discuss the injury of LSECs in liver diseases in this article. Generally, in noninflamed tissues, vascular endothelial cells maintain quiescence of circulating leukocytes, and unnecessary blood clotting is inhibited by multiple antithrombotic factors produced by the endothelial cells. In the setting of inflammation, injured endothelial cells lose these functions, defined as inflammatory endotheliopathy. In chronic hepatitis C, inflammatory endotheliopathy in LSECs contributes to platelet accumulation in the liver tissue, and the improvement of thrombocytopenia by splenectomy is attenuated in cases with severe hepatic inflammation. In COVID-19, LSEC endotheliopathy induced by interleukin (IL)-6 trans-signaling promotes neutrophil accumulation and platelet microthrombosis in the liver sinusoids, resulting in liver injury. IL-6 trans-signaling promotes the expression of intercellular adhesion molecule-1, chemokine (C-X-C motif) ligand (CXCL1), and CXCL2, which are the neutrophil chemotactic mediators, and P-selectin, E-selectin, and von Willebrand factor, which are involved in platelet adhesion to endothelial cells, in LSECs. Restoring LSECs function is important for ameliorating liver injury. Prevention of endotheliopathy is a potential therapeutic strategy in liver disease.

Risk Factors for the Occurrence of Asymptomatic Brain Lesions in Patients with β-Thalassemia: a Systematic Review and Meta-Analysis.

Several factors, including increased platelet aggregation, decreased platelet survival, decreased antithrombotic factors cause a hypercoagulable state in thalassemia patients. This is the first meta-analysis designed to summarize the association of age, splenectomy, gender, and serum ferritin and hemoglobin levels with the occurrence of asymptomatic brain lesions in thalassemia patients using MRI. This systematic review and meta-analysis was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist. We searched four major databases and included eight articles for this review. The quality of the included studies was assessed based on the Newcastle-Ottawa Scale checklist. Meta-analysis was performed using STATA 13. Odds ratio (OR) and standardized mean difference (SMD) were considered as effect sizes for comparing the categorical and continuous variables, respectively. The pooled OR for splenectomy in patients with brain lesions compared to those without lesions was 2.25 (95% CI 1.22 - 4.17, p = 0.01). The pooled analysis for SMD of age between patients with/without brain lesions was statistically significant, 0.4 (95% CI 0.07 - 0.73, p = 0.017). The pooled OR for the occurrence of silent brain lesions was not statistically significant in males compared to females, 1.08 (95% CI 0.62 - 1.87, p = 0.784). The pooled SMD of Hb and serum ferritin in positive brain lesions compared to negatives were 0.01 (95% CI -0.28, 0.35, p = 0.939) and 0.03 (95% CI -0.28, 0.22, p = 0.817), respectively, which were not statistically significant. Older age and splenectomy are risk factors for developing asymptomatic brain lesions in β-thalassemia patients. Physicians should consider a careful assessment of high-risk patients for starting prophylactic treatment.

Rab GTPases as Modulators of Vascular Function.

Rab GTPases, the largest family of small GTPases, are ubiquitously expressed proteins that control various aspects of cellular function, from cell survival to exocytosis. Rabs cycle between the GDP-bound inactive form and the GTP-bound active form. When activated, specific Rab GTPase-positive vesicles mediate cellular networks involved in intracellular trafficking, recycling, and/or exocytosis of cargo proteins. Dysfunctional Rab signaling pathways have been implicated in various disease processes. The precise cellular functions of several members of the Rab GTPase family are still unknown. A lack of pharmacological tools and the lethality of gene knockouts have made more detailed characterizations of their protein interaction networks difficult. Nevertheless, available evidence suggests that these proteins are vital for normal cell function. Endothelial and smooth muscle cells control vascular lumen diameter and modulate blood flow. Endothelial cells also secrete several pro- and antithrombotic factors and vasoactive substances to coordinate local inflammatory responses and angiogenesis. Rab GTPase function in endothelial cells has been relatively well-explored, while only a handful of reports are available on these proteins in vascular smooth muscle. This review summarizes the present knowledge on Rab GTPases in the vasculature.

Antithrombin supplementation for prevention of vascular thrombosis after pediatric liver transplantation

AimsAfter liver transplantation (LT), synthesis of coagulation factors by the graft recovers faster for pro thrombotic than anti thrombotic factors, resulting in a potential pro thrombotic imbalance. We studied the thrombotic and hemorrhagic complications in our pediatric LT series, providing supplementation of fresh frozen plasma (FFP) and/or antithrombin (AT) in the prophylactic antithrombotic regimen. MethodsThis was a retrospective observational single center study. All isolated pediatric LTs performed between 1/11/2009 and 31/12/2019 (n = 181) were included. Postoperatively, in addition to low molecular weight heparin, 22 patients (12%) received FFP (10 ml/kg twice daily for 10 days), 27 patients (15%) were given FFP (reduced duration) and AT (50–100 IU/kg/day if AT activity remained <70%), and 132 (73%) received AT only. Complications, outcome, and coagulation profiles in postoperative days 0–10 were analyzed. ResultsIn all three treatment groups, AT activity normalized by day 4 while prothrombin remained <70% of normal until day 9. Hepatic artery thrombosis (HAT), portal vein thrombosis (PVT), and hemorrhagic complications occurred in 2.8%, 3.3%, and 3.9% of LTs. One- and 5-year patient and graft survival were 88% (±2.4% Standard Error) and 84% (±2.5%), and 86% (±2.6%) and 84% (±2.7%), respectively, without difference between groups. HAT were associated with low AT on days 0 and 1, and PVT with low AT on day 0. ConclusionsLow antithrombin activity after LT was associated with postoperative thromboses. FFP and/or AT supplementation allowed early normalization of AT activity, while thrombotic or hemorrhagic complications were rare, suggesting efficient and safe management of post-LT coagulopathy.

Knockdown and Knockout of Tissue Factor Pathway Inhibitor in Zebrafish.

Tissue factor pathway inhibitor (TFPI) is an anticoagulant that inhibits factor VIIa and Xa in the blood coagulation pathways. TFPI contains three Kunitz domains, K1, K2, and K3. K1 and K2 inhibit factor VIIa and Xa, respectively. However, the regulation of TFPI is poorly studied. Since zebrafish has become an alternate model to discover novel actors in hemostasis, we hypothesized that TFPI regulation could be studied using this model. As a first step, we confirmed the presence of tfpia in zebrafish using reverse transcription polymerase chain reaction. We then performed piggyback knockdowns of tfpia and found increased coagulation activity in tfpia knockdown. We then created a deletion mutation in tfpia locus using the CRISPR/Cas9 method. The tfpia homozygous deletion mutants showed increased coagulation activities similar to that found in tfpia knockdown. Taken together, our data suggest that tfpia is a negative regulator for zebrafish coagulation, and silencing it leads to thrombotic phenotype. Also, the zebrafish tfpia knockout model could be used for reversing this thrombotic phenotype to identify antithrombotic novel factors by the genome-wide piggyback knockdown method.

Comparative Study of Compliance and Factors Affecting Compliance among Commonly Used Drugs in Deep Vein Thrombosis Patients

Objectives: The objective of current research was to identify the compliance of antithrombotic drug (heparin, warfarin and Rivaroxaban) and factors of non-compliance associated with heparin, warfarin and rivaroxaban.&#x0D; Methodology: A cross-sectional, observational study was conducted on patients suffering from Deep Vein Thrombosis (DVT) at government teaching hospital of Larkana. 348 DVT patients were selected by using online sample calculator software. Data was collected by using pre validated questionnaire after taking patient consent; finally the data was analyzed with statistical package of social sciences (SPSS) version 25.&#x0D; Results: The compliance with rivaroxaban was present in 103 (80.5%) patients followed by heparin drug compliance in 95 (74.2%) DVT patients and warfarin drug compliance in 98 (76.6%) DVT patients. Non-compliance factors with rivaroxaban were; cost in 4 (16.0%) patients, polypharmacy in 6 (24.0%) patients, side effects in 4 (16.0%) patients and prolong therapy in 11 (44.0%) patients. Non-compliance factors with heparin were; monitoring in 13 (39.4%) patients, diet restriction in 6 (18.2%) patients, injectable in 10 (30.3%) patients and ADR in 4 (12.1%) patients. Non-compliance factors with warfarin were; cost in 4 (13.3%) patients, polypharmacy in 8 (26.7%) patients, prolong therapy in 5 (16.7%) patients and ADR in 13 (43.3%) patients. &#x0D; Conclusion: This study concludes that rate of drug compliance was high in patients of DVT with rivaroxaban followed by warfarin and heparin, whereas long duration of therapy, polypharmacy, side effects of therapy, cost of therapy, continuous monitoring, injectables, diet restrictions and ADRs of therapy were the most commonly reported factors of non-compliance.

A young woman presented with massive pulmonary embolism with inferior vena cava thrombus as a complication of nephrotic syndrome: a case report

Nephrotic syndrome (NS) was first described in 1827 as the presence of proteinuria of ≥ 3.5 g/24 h, hypoalbuminemia < 3.0 g/dl, peripheral edema, hyperlipidemia, lipiduria, and increased thrombotic risk. Nephrotic syndrome has an incidence of three cases per 100,000 each year in adults. Nephrotic syndrome also has serious complications due to hypercoagulable state in both various venous and arteries which could lead thromboembolic events. The pathophysiology of hypercoagulability in the nephrotic syndrome is due to an imbalance of prothrombotic and antithrombotic factors, as well as impaired thrombolytic activities.Here, we will present a 19-year-old woman who presented to the emergency department complaining of chest pain and shortness of breath for 3 days. The patient was quickly diagnosed with pulmonary embolism and inferior vena cava thrombosis as a complication of nephrotic syndrome, allowing prompt initiation of anticoagulant therapy. After 2 weeks of admission, the patient’s condition resolved, her laboratory results returned to almost normal and the patient was discharged with oral prednisolone, coumadin, atorvastatin, and ramipril. We aim to determine which is the likely cause of pulmonary embolism in patients with nephrotic syndrome.

Efficacy and safety of plasma hemodiafiltration (PHDF) in pediatric patients with multiple organ dysfunction syndrome with shock and DIC: a preliminary study

BackgroundMultiple organ dysfunction syndrome is the leading cause of death in pediatric intensive care units and can be very critical when combined with shock and disseminated intravascular coagulation (DIC). Currently, there is no effective treatment. We developed a new hemodiafiltration (HDF) method called plasma HDF (PHDF) that uses fresh frozen plasma as replacement fluid and investigated the safety and efficacy of this treatment.MethodsWe enrolled critically ill children with (1) a Pediatric Logistic Organ Dysfunction 2 (PELOD-2) score ≥ 14, (2) a Japanese Ministry of Health and Welfare (JMHW) DIC score ≥ 7, (3) a vasoactive inotropic score (VIS) ≥ 10, and (4) a serum total protein concentration ≤ 5.0 g/dL. PHDF was performed for 5 h and then switched to continuous HDF. The primary endpoint was the 28-day mortality rate. Secondary endpoints included assessment of vital signs, blood test data, and fluid balance from PHDF start to day 7.ResultsNine patients (four males and five females) between 3 days and 40 months of age, weighing 2.1–13 kg, met the inclusion criteria. Although the median PMR was 0.94 (0.71–0.96), the 28-day mortality rate was 22.2% (2/9). One hour after the start of PHDF, there was an increase in mean arterial pressure and central venous pressure and a decrease in heart rate; by day 7, there was a significant decrease in the PELOD-2 score, the JMHW DIC score, and the VIS. Hypoproteinemia also improved the day after PHDF. Water balance was able to remain negative after day 2.ConclusionsPHDF was found to be effective in the treatment of DIC and circulatory failure by supplementing coagulation and antithrombotic factors as well as by raising colloid osmotic pressure to increase circulating blood volume. PHDF has been shown to be a safe and useful treatment for critically ill children and has the potential to improve 28-day survival.

Cancer and thrombosis: new insights to an old problem.

Venous thromboembolism (VTE) is a common complication in patients with cancer and portends a poor prognosis. Our understanding of the underlying pathophysiology of VTE in cancer has advanced since Trousseau first described hypercoagulability in patients with malignancy and Virchow described his famous triad of thrombosis formation. Malignancy itself induces a thrombophilic state by increasing the risk of venous stasis, endothelial injury and an imbalance of pro and anti-thrombotic factors leading to a hypercoaguable state. Additional insults to this thrombotic balance are introduced by patient-specific, treatment related and tumor-specific factors. The importance of understanding the factors associated with increased thrombosis in cancer is paramount in order to adequately identify patients who will benefit from thromboprophylaxis.

Congenital Multiple Antithrombotic Factors Deficiency in Neonate: A Rare Case Report

Congenital Multiple Antithrombotic Factors Deficiency in Neonate: A Rare Case Report

Anticoagulation Increases Bleeding Rates in Portal Vein Thrombosis: A National Database Study

Introduction: Liver cirrhosis is being increasingly recognized as a hypercoagulable state, mainly due to disproportionate reduction in antithrombotic factors (protein C, S and anti-thrombin III). Portal vein thrombosis (PVT) is a frequent sequala of liver cirrhosis that can lead to numerous complications and potential exclusion from transplant lists, at least until the resolution of the thrombus. The current evidence for anticoagulation (AC) for PVT in liver cirrhosis is limited to small retrospective studies. Major liver societies recommend limited anticoagulation with enoxaparin based on expert opinion (Category C). We sought to examine the incidence of bleeding after AC in cirrhotic patients with PVT. Methods: Data were obtained from a commercial de-identified database (Explorys, IBM, Inc.) that integrates electronic health records from 27 major integrated U.S. healthcare systems from 1999 to July 2019. Cases were defined as adult patients aged &gt;=18 years having a new Systematized Nomenclature of Medicine Clinical Terms (SNOMED) diagnosis of PVT, had been anticoagulated for the first time following PVT and had experienced bleeding for the first time following AC. Controls were adults who had a diagnosis of PVT and did not get AC. We included older anticoagulants (warfarin and enoxaparin) as well as newer anticoagulants (apixaban, fondaparinux and rivaroxaban). We compared the incidence of bleeding (defined as bleeding from any site) in those with PVT who received AC to those with PVT who did not receive AC. In addition, we also compared the incidence of bleeding between older and newer anticoagulants, and also examined whether there were differences in gender, race, and insurance status for those who bled while on AC. Analysis comprised of calculating odds ratios (OR) and confidence intervals (CI) for the OR. Results: A total of 213,810 patients had liver cirrhosis and out of those, 7,570 (3.5%) patients had PVT. Four hundred and ten cases out of 1,430 patients who received AC bled for the first time whereas 980 cases out of 3,880 patients who did not receive AC bled for the first time. Cases on AC had 1.18 times higher odds of bleeding when compared to controls who did not receive AC (CI = 1.04 - 1.36). Newer AC were less likely to increase bleeding when compared to older AC (OR = 0.6, CI = 0.4 - 0.9). Females were significantly more likely to be first time bleeders on AC when compared to male first-time bleeders on AC (Table 1). However, race and insurance status did not seem to affect bleeding rates (Table 1). Conclusion: Anticoagulation for PVT in liver cirrhosis increases bleeding events. Newer AC were significantly less likely to increase bleeding when compared to older AC. Females were more likely to bleed on newer AC than males, but race and insurance status did not affect bleeding rates. Limitations of the study include the retrospective nature of the analysis that relied on diagnosis coding, and smaller numbers in our subgroup analyses which limits generalizability. Clinicians should be aware of the significant risk of bleeding when prescribing AC, particularly older AC to cirrhotic patients with PVT. Disclosures No relevant conflicts of interest to declare.

Wall Shear Stress in the Middle Cerebral Artery of HM II Patients - A Prospective, Mechanistic Study Using Vector Flow Mapping

Purpose It has been proposed that the high prevalence of bleeding events in continuous-flow left ventricular assist device (CF-LVAD) patients may be lowered by increasing von Willebrand factor-release via augmented peripheral pulsatility (PI). However, the hemostatic effects of increased PI may be offset by concomitant increases in local wall shear stress (WSS) - which is known to stimulate the endothelial release of anti-thrombotic factors (NO, prostacyclin, thrombomodulin). Hypothesis Higher pulsatility in the middle cerebral artery of CF-LVAD patients will be significantly associated with increased local WSS. Methods Video loops of color Doppler recordings from the middle cerebral artery were obtained in 8 HeartMate II (HM II) patients and 8 healthy controls. Data were analyzed offline with validated vector flow mapping software. WSS was calculated as: viscosity*(du/dy), according to Newton's law. Viscosity was corrected by using individuals’ hematocrit. Importantly, we determined not only peak WSS but also WSS per beat (area under the curve) and WSS/min (WSS/beat * heart rate). PI was measured from angle-corrected pulsed-wave Doppler velocities. Results Peak WSS and WSS/beat were lower in HM II (P = 0.05) but WSS/min was not different (P > 0.05). Supporting our hypothesis, WSS and pulsatility index (PI) were strongly correlated non-linearly in HM II patients (r2 = 0.94) and shared a common linear slope with healthy controls between a PI of ∼0.45 and ∼0.90 (Fig. 1). Conclusion In CF-LVAD patients, a strong curvilinear relationship was noted between cerebral PI and WSS, with linear increases in WSS shown above a PI of ∼0.45. These data suggest a threshold for PI and its interaction with endothelium-dependent hemostatic and anti-thrombotic activity. Future work is warranted to investigate whether alteration of the PI-WSS relationship will influence the release of hemostatic or anti-thrombotic factors and reduce cerebral bleeding in CF-LVAD patients.

¿Proteínas de origen vegetal o de origen animal?: Una mirada a su impacto sobre la salud y el medio ambiente

Adequate protein intake is crucial for the optimal functioning&nbsp;of the body. Depending on their source, proteins may be&nbsp;of animal or plant origin. The former are an excellent source of&nbsp;zinc, heme iron, B vitamins and essential amino acids, are more&nbsp;easily digested and provide all essential amino acids. However,a high intake of animal proteins is associated with an increased&nbsp;risk of mortality and development of cardiovascular health&nbsp;complications. Although plant-based proteins are often perceived&nbsp;as an incomplete protein source because they contain little&nbsp;or no limiting aminoacids, it is possible to obtain high qualityproteins from a combination of plant sources. Both animal and&nbsp;vegetable proteins are rich in functional peptides that can act as&nbsp;an immune modulating, antithrombotic, hypocholesterolemic&nbsp;and other factors. The production of vegetable proteins implies&nbsp;a considerably smaller environmental impact, in comparison&nbsp;with the production of proteins of animal origin. Therefore, it&nbsp;is necessary to advance in the production and promotion of alternative&nbsp;foods, a source of vegetable protein, that supply the&nbsp;nutritional needs of the population and reduce the cost to the&nbsp;environment associated with the production and consumption&nbsp;of animal protein.

Peroxisome proliferator-activated receptor α attenuates high-cholesterol diet-induced toxicity and pro-thrombotic effects in mice.

Peroxisome proliferator-activated receptor α (PPARα) is involved in the regulation of fatty acid and cholesterol metabolism. A high-cholesterol (HC) diet increases the risk of developing cardiovascular diseases (CVD); however, it is unclear whether the toxic effects of cholesterol involve changes in thrombotic factor expression, and whether PPARα is necessary for such effects. To investigate this possibility, we fed a HC diet to wild-type (WT) and Ppara-null mice and measured cholesterol and triglyceride contents, liver histology, serum/plasma levels of coagulation factors, hepatic expression of the coagulation factors, liver/serum sulfatide levels, hepatic sulfatide metabolism, hepatic expression of lipid transporters, and hepatic oxidative stress and its relating enzymes. In Ppara-null mice, the HC diet caused triglyceride accumulation and exacerbated inflammation and oxidative stress in liver, increased levels of coagulation factors, including tissue factor, plasminogen activator inhibitor-1 and carboxypeptidase B2 in blood and liver, and decreased levels of anti-thrombotic sulfatides in serum and liver. These changes were much less marked in WT mice. These findings imply that cholesterol overload exerts its toxic effects at least in part by enhancing thrombosis, secondary to abnormal hepatic lipid metabolism, inflammation, and oxidative stress. Moreover, we reveal for the first time that PPARα can attenuate these toxic effects by transcriptional regulation of coagulation factors and sulfatides, in addition to its known effects of controlling lipid homeostasis and suppressing inflammation and oxidative stress. Therapies aimed at activating PPARα might prevent HC diet-induced CVD through modulating various pro- and anti-thrombotic factors.

Poorly Controlled Homocystinuria: A Rare Cause of Ischemic Priapism?

We report on the 1st case of ischemic priapism secondary to poorly controlled homocystinuria. Homocystinuria is a rare, autosomal recessive, inherited disorder of metabolism that is caused by a deficiency of cystathionine synthase, leading to marked hyperhomocysteinemia. Arterial and/or venous thromboemboli are a major cause of mortality and morbidity in patients with homocystinuria. Untreated patients have a 50% chance of having a vascular event by 30 years of age. Increased homocysteine levels have been reported to upregulate prothrombotic factors and downregulate antithrombotic factors; in particular, increased homocystinuria has been found to downregulate nitric oxide (NO). Mice that are deficient in NO synthase in the cavernosal smooth muscles have a higher incidence of priapism. Decrease in NO synthase causes downregulation of cyclic guanosine monophosphate, phosphodiesterase type 5A, and Rho A/Rho-kinase. Because persistently increased homocysteine also downregulates NO, a similar mechanism could be proposed for priapism secondary to homocystinuria. In patients presenting with priapism, specific features of homocystinuria should be sought; in selected patients, screening with plasma total homocysteine might be appropriate. Ischemic priapism secondary to homocystinuria appears to respond well to the standard treatment options of aspiration, intracavernosal injection with phenylephrine, and, if required, a shunting procedure.Johnson M, Murphy E, Raheem A, Ralph D. Poorly Controlled Homocystinuria: A Rare Cause of Ischemic Priapism? Sex Med 2018;6:171–173.

Altered Redox Balance in the Development of Chronic Hypoxia-induced Pulmonary Hypertension.

Normally, the pulmonary circulation is maintained in a low-pressure, low-resistance state with little resting tone. Pulmonary arteries are thin-walled and rely heavily on pulmonary arterial distension and recruitment for reducing pulmonary vascular resistance when cardiac output is elevated. Under pathophysiological conditions, however, active vasoconstriction and vascular remodeling lead to enhanced pulmonary vascular resistance and subsequent pulmonary hypertension (PH). Chronic hypoxia is a critical pathological factor associated with the development of PH resulting from airway obstruction (COPD, sleep apnea), diffusion impairment (interstitial lung disease), developmental lung abnormalities, or high altitude exposure (World Health Organization [WHO]; Group III). The rise in pulmonary vascular resistance increases right heart afterload causing right ventricular hypertrophy that can ultimately lead to right heart failure in patients with chronic lung disease. PH is typically characterized by diminished paracrine release of vasodilators, antimitogenic factors, and antithrombotic factors (e.g., nitric oxide and protacyclin) and enhanced production of vasoconstrictors and mitogenic factors (e.g., reactive oxygen species and endothelin-1) from the endothelium and lung parenchyma. In addition, phenotypic changes to pulmonary arterial smooth muscle cells (PASMC), including alterations in Ca2+ homeostasis, Ca2+ sensitivity, and activation of transcription factors are thought to play prominent roles in the development of both vasoconstrictor and arterial remodeling components of hypoxia-associated PH. These changes in PASMC function are briefly reviewed in Sect. 1 and the influence of altered reactive oxygen species homeostasis on PASMC function discussed in Sects. 2-4.