Search results for " CARDIOVASCULAR"

NOX2ko Mice Show Largely Increased Expression of a Mutated NOX2 mRNA Encoding an Inactive NOX2 Protein

2020

Background: The superoxide-generating enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2 or gp91phox, the phagocytic isoform) was reported as a major source of oxidative stress in various human diseases. Genetic deletion is widely used to study the impact of NOX2-derived reactive oxygen species (ROS) on disease development and progression in various animal models. Here, we investigate why NOX2 knockout mice show no NOX2 activity but express NOX2 mRNA and protein. Methods and Results: Oxidative burst (NOX2-dependent formation of ROS) was measured by L-012-based chemiluminescence and was largely absent in whole blood of NOX2 knockout mice. Protein expression was still de…

Assessing sensory versus optogenetic network activation by combining (o)fMRI with optical Ca2+ recordings

2016

Encoding of sensory inputs in the cortex is characterized by sparse neuronal network activation. Optogenetic stimulation has previously been combined with fMRI (ofMRI) to probe functional networks. However, for a quantitative optogenetic probing of sensory-driven sparse network activation, the level of similarity between sensory and optogenetic network activation needs to be explored. Here, we complement ofMRI with optic fiber-based population Ca2+ recordings for a region-specific readout of neuronal spiking activity in rat brain. Comparing Ca2+ responses to the blood oxygenation level-dependent signal upon sensory stimulation with increasing frequencies showed adaptation of Ca2+ transient…

Genetics and Gene Therapy of Anderson-Fabry Disease.

2018

Fabry's disease is a genetic disorder of X-linked inheritance caused by mutations in the alpha galactosidase A gene resulting in deficiency of this lysosomal enzyme. The progressive accumulation of glycosphingolipids, caused by the inadequate enzymatic activity, is responsible of organ dysfunction and thus of clinical manifestations. In the presence of a high clinical suspicion, a careful physical examination and specific laboratory tests are required, finally diagnosis of Fabry's disease is confirmed by the demonstration of absence or reduced alpha-galactosidase A enzyme activity in hemizygous men and gene typing in heterozygous females; in fact the performance of enzymatic activity assay …

Molecular disturbance underlies to arrhythmogenic cardiomyopathy induced by transgene content, age and exercise in a truncated PKP2 mouse model

2016

13 páginas, 9 tablas, 2 figuras. Contiene material suplementario.

2020

Lipoprotein(a) [Lp(a)] is a major cardiovascular risk factor, which is largely genetically determined by one major gene locus, the LPA gene. Many aspects of the transcriptional regulation of LPA are poorly understood and the role of epigenetics has not been addressed yet. Therefore, we conducted an epigenome-wide analysis of DNA methylation on Lp(a) levels in two population-based studies (total n = 2208). We identified a CpG site in the LPA promoter which was significantly associated with Lp(a) concentrations. Surprisingly, the identified CpG site was found to overlap the SNP rs76735376. We genotyped this SNP de-novo in three studies (total n = 7512). The minor allele of rs76735376 (1.1% mi…

Basic Concepts in Molecular Biology Related to Genetics and Epigenetics.

2017

The observation that "one size does not fit all" for the prevention and treatment of cardiovascular disease, among other diseases, has driven the concept of precision medicine. The goal of precision medicine is to provide the best-targeted interventions tailored to an individual's genome. The human genome is composed of billions of sequence arrangements containing a code that controls how genes are expressed. This code depends on other nonstatic regulators that surround the DNA and constitute the epigenome. Moreover, environmental factors also play an important role in this complex regulation. This review provides a general perspective on the basic concepts of molecular biology related to g…

Targeting aging with functional food: Pasta with opuntia single-arm pilot study

2018

Interventions to extend life span represent the new perspective in aging investigation. Healthy dietary habits are important modifiable factors that can favor a healthy aging phenotype. Many studies have demonstrated benefits for metabolic syndrome and type 2 diabetes mellitus resulting from the traditional Mediterranean foods. Opuntia Ficus Indica (OFI), widespread in the Mediterranean basin, belongs to the Cactaceae family. It is known for its antioxidant and anti-inflammatory properties. Moreover, products containing extracts from OFI fruits or cladodes have been used to control obesity and other metabolic parameters, such as glycemia and lipid profile. The aim of this study was to analy…

Association of leisure time physical activity and NMR-detected circulating amino acids in peripubertal girls: A 7.5-year longitudinal study

2017

AbstractThis study investigated the longitudinal associations of physical activity and circulating amino acids concentration in peripubertal girls. Three hundred ninety-six Finnish girls participated in the longitudinal study from childhood (mean age 11.2 years) to early adulthood (mean age 18.2 years). Circulating amino acids were assessed by nuclear magnetic resonance spectroscopy. LTPA was assessed by self-administered questionnaire. We found that isoleucine, leucine and tyrosine levels were significantly higher in individuals with lower LTPA than their peers at age 11 (p < 0.05 for all), independent of BMI. In addition, isoleucine and leucine levels increased significantly (~15%) fro…

How can dementia and disability be prevented in older adults: where are we today and where are we going?

2021

Abstract Ageing of the population, together with population growth, has brought along an ample increase in the number of older individuals living with dementia and disabilities. Dementia is the main cause of disability in old age, and promoting healthy brain ageing is considered as a key element in diminishing the burden of age‐related disabilities. The World Health Organization recently launched the first risk reduction guidelines for cognitive impairment and dementia. According to recent estimates, approximately 40% of dementia cases worldwide could be attributable to 12 modifiable risk factors: low education; midlife hypertension and obesity; diabetes, smoking, excessive alcohol use, phy…

Endothel, vaskuläre Funktion und COVID-19

2020

ZusammenfassungSeit Beginn der COVID-19-Pandemie konnten zahlreiche Erkenntnisse über den 3-phasigen Verlauf einer SARS-CoV-2-Infektion, den Infektionsweg und die Bedeutung einer vaskulären Dysfunktion gewonnen werden. Im Rahmen der Infektion kann es zu einer hyperinflammatorischen Phase mit sekundären Organschäden bis hin zum Tod kommen. Diese schweren Krankheitsverläufe gehen mit einer unkontrollierten Freisetzung von Entzündungsmediatoren und Zytokinen einher. Auf zellulärer Ebene bedingt der membrangebundene ACE-2-Rezeptor die Invasion des Virus und stimuliert über einen 2. Mechanismus die Metalloprotease ADAM17 sowie die Freisetzung von Zytokinen. Vasokonstriktive Veränderungen sowie d…