Perspectives on Cognitive Phenotypes and Models of Vascular Disease

Clinical investigations have established that vascular-Associated medical conditions are significant risk factors for various kinds of dementia. And yet, we are unable to associate certain types of vascular deficiencies with specific cognitive impairments. The reasons for this are many, not the least of which are that most vascular disorders are multi-factorial and the development of vascular dementia in humans is often a multi-year or multi-decade progression. To better study vascular disease and its underlying causes, the National Heart, Lung, and Blood Institute of the National Institutes of Health has invested considerable resources in the development of animal models that recapitulate various aspects of human vascular disease. Many of these models, mainly in the mouse, are based on genetic mutations, frequently using single-gene mutations to examine the role of specific proteins in vascular function. These models could serve as useful tools for understanding the association of specific vascular signaling pathways with specific neurological and cognitive impairments related to dementia. To advance the state of the vascular dementia field and improve the information sharing between the vascular biology and neurobehavioral research communities, National Heart, Lung, and Blood Institute convened a workshop to bring in scientists from these knowledge domains to discuss the potential utility of establishing a comprehensive phenotypic cognitive assessment of a selected set of existing mouse models, representative of the spectrum of vascular disorders, with particular attention focused on age, sex, and rigor and reproducibility. The workshop highlighted the potential of associating well-characterized vascular disease models, with validated cognitive outcomes, that can be used to link specific vascular signaling pathways with specific cognitive and neurobehavioral deficits

Mapping the lymphatic system across body scales and expertise domains: A report from the 2021 National Heart, Lung, and Blood Institute workshop at the Boston Lymphatic Symposium

Enhancing our understanding of lymphatic anatomy from the microscopic to the anatomical scale is essential to discern how the structure and function of the lymphatic system interacts with different tissues and organs within the body and contributes to health and disease. The knowledge of molecular aspects of the lymphatic network is fundamental to understand the mechanisms of disease progression and prevention. Recent advances in mapping components of the lymphatic system using state of the art single cell technologies, the identification of novel biomarkers, new clinical imaging efforts, and computational tools which attempt to identify connections between these diverse technologies hold the potential to catalyze new strategies to address lymphatic diseases such as lymphedema and lipedema. This manuscript summarizes current knowledge of the lymphatic system and identifies prevailing challenges and opportunities to advance the field of lymphatic research as discussed by the experts in the workshop

Point-of-Care Technologies for Precision Cardiovascular Care and Clinical Research

Point-of-care technologies (POC or POCT) are enabling innovative cardiovascular diagnostics that promise to improve patient care across diverse clinical settings. The National Heart, Lung, and Blood Institute convened a working group to discuss POCT in cardiovascular medicine. The multidisciplinary working group, which included clinicians, scientists, engineers, device manufacturers, regulatory officials, and program staff, reviewed the state of the POCT field; discussed opportunities for POCT to improve cardiovascular care, realize the promise of precision medicine, and advance the clinical research enterprise; and identified barriers facing translation and integration of POCT with existing clinical systems. A POCT development roadmap emerged to guide multidisciplinary teams of biomarker scientists, technologists, health care providers, and clinical trialists as they: 1) formulate needs assessments; 2) define device design specifications; 3) develop component technologies and integrated systems; 4) perform iterative pilot testing; and 5) conduct rigorous prospective clinical testing to ensure that POCT solutions have substantial effects on cardiovascular care

Vascular contributions to cognitive impairment and dementia including Alzheimer's disease

AbstractScientific evidence continues to demonstrate the linkage of vascular contributions to cognitive impairment and dementia such as Alzheimer's disease. In December, 2013, the Alzheimer's Association, with scientific input from the National Institute of Neurological Disorders and Stroke and the National Heart, Lung and Blood Institute from the National Institutes of Health, convened scientific experts to discuss the research gaps in our understanding of how vascular factors contribute to Alzheimer's disease and related dementia. This manuscript summarizes the meeting and the resultant discussion, including an outline of next steps needed to move this area of research forward

Treatment for Mild Chronic Hypertension during Pregnancy.

BACKGROUND: The benefits and safety of the treatment of mild chronic hypertension (blood pressure, \u3c160/100 mm Hg) during pregnancy are uncertain. Data are needed on whether a strategy of targeting a blood pressure of less than 140/90 mm Hg reduces the incidence of adverse pregnancy outcomes without compromising fetal growth. METHODS: In this open-label, multicenter, randomized trial, we assigned pregnant women with mild chronic hypertension and singleton fetuses at a gestational age of less than 23 weeks to receive antihypertensive medications recommended for use in pregnancy (active-treatment group) or to receive no such treatment unless severe hypertension (systolic pressure, ≥160 mm Hg; or diastolic pressure, ≥105 mm Hg) developed (control group). The primary outcome was a composite of preeclampsia with severe features, medically indicated preterm birth at less than 35 weeks\u27 gestation, placental abruption, or fetal or neonatal death. The safety outcome was small-for-gestational-age birth weight below the 10th percentile for gestational age. Secondary outcomes included composites of serious neonatal or maternal complications, preeclampsia, and preterm birth. RESULTS: A total of 2408 women were enrolled in the trial. The incidence of a primary-outcome event was lower in the active-treatment group than in the control group (30.2% vs. 37.0%), for an adjusted risk ratio of 0.82 (95% confidence interval [CI], 0.74 to 0.92; P CONCLUSIONS: In pregnant women with mild chronic hypertension, a strategy of targeting a blood pressure of less than 140/90 mm Hg was associated with better pregnancy outcomes than a strategy of reserving treatment only for severe hypertension, with no increase in the risk of small-for-gestational-age birth weight. (Funded by the National Heart, Lung, and Blood Institute; CHAP ClinicalTrials.gov number, NCT02299414.)

Distribution of endogenous lipoproteins and sulfated proteoglycans in normal rabbit aorta and in atherosclerotic lesions induced by endothelial injury

Note:The effects of an endothelial injury, produced by balloon catheterization of the aorta in normocholesterolemic rabbits, were studied by immunocytochemical and biochemical methods. Apolipoprotein B (apo B), as a marker for endogenous lipoproteins (LP), was detected by quantitative gold immunocytochemistry. In contrast to normal aortas, where apo B distribution was limited to the innermost regions, in previously injured aortas, apo B accumulated in advanced lesions developed under the regenerated endothelium, both in the extracellular space and inside foam cells, demonstrating the atherosclerotic nature of the lesions. In order to establish the putative role of chondroitin sulfate (CS) proteoglycans (PG), known for their great in vitro affinity for LP, the overall and ultrastructural distribution, as well as the biochemical properties of CS-PG molecules extracted from normal and injured aortas were examined. […]Le projet concerne l'étude du rôle qu'une lésion de l'endothélium vasculaire peut jouer dans le développement de lésions athéromateuses. Les lésions sont obtenues expérimentalement chez le lapin suite à la cathéterisation de l'aorte. La distribution des lipoprotéines (LP) endogènes considérées athérogènes, détectées par un anticorps qui reconnait l'apolipoprotéine B (apo B) de lapin, a été étudiée par immunocytochimie ultrastructurelle quantitative à l'or colloïdal, dans des tissus provenant des aortes normales ou lésées. Dans les aortes normales, la distribution de l'apo Best restreinte a la couche endothéliale. Par contraste, dans les aortes lésées l'apo Best accumulée dans les lésions développées sous l'endothélium régénère, autant dans l'espace intercellulaire que dans les cellules, confirmant leur nature athéromateuse. Les caractéristiques biochimiques et morphologiques des proteoglycanes (PG) contenant des chaines de sulfate de chondroïtine, qui interagissent avec grande affinité avec LP in vitro, et on suppose par conséquent qu'ils soient aussi responsables de leur immobilisation dans les lésions athéromateuses, ont été analysées dans des tissus provenant des aortes normales ou lésées. […