A molecular complex of Cav1.2/CaMKK2/CaMK1a in caveolae is responsible for vascular remodeling via excitation–transcription coupling

Elevation of intracellular Ca2+ concentration ([Ca2+]i) activates Ca2+/calmodulin-dependent kinases (CaMK) and promotes gene transcription. This signaling pathway is referred to as excitation–transcription (E-T) coupling. Although vascular myocytes can exhibit E-T coupling, the molecular mechanisms and physiological/pathological roles are unknown. Multiscale analysis spanning from single molecules to whole organisms has revealed essential steps in mouse vascular …

Continue reading A molecular complex of Cav1.2/CaMKK2/CaMK1a in caveolae is responsible for vascular remodeling via excitation–transcription coupling

First time detection of the vaccine spike protein in a person who died after vaccination against Covid-19.

The suspicion that the spike protein formed in the body as a result of the "vaccination" against Covid-19 could be responsible for the pathologically observed inflammations and lesions of vessels has now been confirmed immunohistologically for the first time. The pathologists Prof. Dr. Arne Burkhardt and Prof. Dr. Walter Lang and their team have succeeded …

Continue reading First time detection of the vaccine spike protein in a person who died after vaccination against Covid-19.

Ankle‐Brachial Index and Subsequent Risk of Severe #Ischemic #Leg Outcomes: The ARIC Study

Ankle‐brachial index (ABI) is used to identify lower‐extremity peripheral artery disease (PAD). However, its association with severe ischemic leg outcomes (eg, amputation) has not been investigated in the general population. Methods and ResultsAmong 13 735 ARIC (Atherosclerosis Risk in Communities) study participants without clinical manifestations of PAD (mean age, 54 [SD, 5.8] years; 44.4% men; …

Continue reading Ankle‐Brachial Index and Subsequent Risk of Severe #Ischemic #Leg Outcomes: The ARIC Study

Trimethylamine-N-Oxide Promotes Age-Related Vascular Oxidative Stress and Endothelial Dysfunction in Mice and Healthy Humans

Age-related vascular endothelial dysfunction is a major antecedent to cardiovascular diseases. We investigated whether increased circulating levels of the gut microbiome-generated metabolite trimethylamine-N-oxide induces endothelial dysfunction with aging. In healthy humans, plasma trimethylamine-N-oxide was higher in middle-aged/older (64±7 years) versus young (22±2 years) adults (6.5±0.7 versus 1.6±0.2 µmol/L) and inversely related to brachial artery flow-mediated …

Continue reading Trimethylamine-N-Oxide Promotes Age-Related Vascular Oxidative Stress and Endothelial Dysfunction in Mice and Healthy Humans

IFN-γ drives inflammatory bowel disease pathogenesis through VE-cadherin–directed #vascular barrier disruption

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with rising incidence. Diseased tissues are heavily vascularized ..Specifically, we show that inhibition of the IFN-γ response in vessels by endothelial-specific knockout of IFN-γ receptor 2 ameliorates experimentally induced colitis in mice. IFN-γ acts pathogenic by causing a breakdown of the vascular barrier through disruption of …

Continue reading IFN-γ drives inflammatory bowel disease pathogenesis through VE-cadherin–directed #vascular barrier disruption