Adrenoceptor-stimulated inflammatory response in stress-induced serum amyloid A synthesis

Rationale Stressful life events are suggested to contribute to the development of various pathologies, such as cardiovascular disorders, whose etiopathogenesis is highly associated with elevated levels of serum amyloid A (SAA) proteins. SAA synthesis inthe liver isregulated bya complex network ofcytokines actingindependently orinconcert withvarious hormones/stimulants including the stress-activated sympathetic nervous system. Objective This study aims to investigate the underlying mechanisms that regulate the stress-induced hepatic synthesis of SAA, with particular focus on adrenoceptors (AR), major components of the sympathoadrenal response to stress. Methods and results We demonstrated that repeated stress elevates IL-1β, IL-6, and TNFα serum levels in mice, accompanied by increased synthesis and secretion of hepatic SAA1/2 and SAA3, an effect that was blocked by AR antagonists. Moreover, stimulation ofα1- andβ1/2-ARsmimics thestress effectonSAA1/2 regulation, whereas α2-AR stimulation exhibitsa relatively weakimpactonSAA.InsupportoftheessentialcytokinecontributionintheAR-agonistinducedSAAproductionisthefactthat theanti-inflammatorydrug,sodiumsalicylate,preventedtheAR-stimulatedhepaticSAA1/2synthesisbyreducingIL-1βlevels, whereasIL-1βinhibitionwithAnakinramimicsthissodiumsalicylatepreventiveeffect,thusindicatingacrucial rolefor IL-1β. Interestingly, the AR-driven SAA3 synthesis was elevated by sodium salicylate in a TNFα-dependent way, supporting diverse and complex regulatory roles of cytokines in SAA production. In contrast to α1/α2-AR, the β1/2-AR-mediated SAA1/2 and SAA3 upregulation cannot be reversed by fenofibrate, a hypolipidemic drug with anti-inflammatory properties. Conclusion Taken together, these findings strongly support a critical role of the AR-stimulated inflammatory response in the hepatic SAA production under stressful conditions, highlighting distinct AR type-specific mechanisms that regulate the hepatic synthesis of SAA1/2 and SAA3.This research was supported by the European Union (European Regional Development Fund-ERDF) and the Greek national funds through the Operational Program "THESSALY-MAINLAND GREECE AND EPIRUS-2007-2013" of the National Strategic Reference Framework (NSRF 2007-2013, Grant 346985/80753) and the National Cancer Institute Intramural Research Program.info:eu-repo/semantics/publishedVersio

Adrenoceptor‐related decrease in serum triglycerides is independent of PPARα activation

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151956/1/febs14966.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151956/2/febs14966_am.pd

Derivation of relativistic SEP properties through neutron monitor data modeling

The Ground Level Enhancement (GLE) data recorded by the worldwide Neutron Monitor (NM) network are useful resources for space weather modeling during solar extreme events. The derivation of Solar Energetic Particles (SEPs) properties through NM-data modeling is essential for the study of solar-terrestrial physics, providing information that cannot be obtained through the exclusive use of space techniques; an example is the derivation of the higher-energy part of the SEP spectrum. We briefly review how the application of the Neutron Monitor Based Anisotropic GLE Pure Power Law (NMBANGLE PPOLA) model (Plainaki et al. 2010), can provide the characteristics of the relativistic SEP flux, at a selected altitude in the Earth's atmosphere, during a GLE. Technically, the model treats the NM network as an integrated omnidirectional spectrometer and solves the inverse problem of the SEP-GLE coupling. As test cases, we present the results obtained for two different GLEs, namely GLE 60 and GLE 71, occurring at a temporal distance of ~ 11 years

Unraveling the role of resistin, retinol-binding protein 4 and adiponectin produced by epicardial adipose tissue in cardiac structure and function: evidence of a paracrine effect

PurposeAdipokines produced by adipose tissue have been found to be involved in the pathophysiology of metabolic and cardiovascular diseases. We aimed to investigate the relationships of resistin, retinol-binding protein 4 (RBP4) and adiponectin produced by epicardial adipose tissue with coronary artery disease (CAD) and cardiac structure and function.MethodsForty-one non-diabetic males scheduled for cardiothoracic surgery were examined. Anthropometric measurements, echocardiography, coronary angiography, and blood analysis were performed preoperatively. We measured the serum levels of resistin, RBP4, and adiponectin and their mRNA expression in thoracic subcutaneous adipose tissue and two epicardial adipose tissue samples, one close to left anterior descending artery (LAD) (resistin-LAD, RBP4-LAD, adiponectin-LAD), and another close to the right coronary artery (RCA) (resistin-RCA, RBP4-RCA, adiponectin-RCA).ResultsLeft ventricular (LV) ejection fraction correlated negatively with adiponectin-LAD (rho = - 0.390, p = 0.025). The ratio of early to late diastolic transmitral flow velocity, as an index of LV diastolic function, correlated negatively with resistin-LAD (rho = - 0.529, p = 0.024) and RBP4-LAD (rho = - 0.458, p = 0.049). There was no difference in epicardial adipose tissue mRNA expression of resistin, RBP4, and adiponectin between individuals with CAD and those without CAD. When we compared the individuals with CAD in the LAD with those without CAD in the LAD, there was no difference in resistin-LAD, RBP4-LAD, and adiponectin-LAD. There was no difference in resistin-RCA, RBP4-RCA, and adiponectin-RCA between the individuals with CAD in the RCA and those without CAD in the RCA.ConclusionElevation of epicardial adipose tissue mRNA expression of adiponectin was associated with LV systolic dysfunction, while that of both resistin and RBP4 was linked to LV diastolic dysfunction