20 research outputs found
Innate and Adaptive Inflammation as a Therapeutic Target in Vascular Disease The Emerging Role of Statins
Atherosclerosis, the main pathophysiological condition leading to cardiovascular disease (CVD), is now considered to be a chronic inflammatory condition. Statins are the most widely used and promising agents in treating CVD and are renowned for their pleiotropic lipid-lowering independent effects. Statins exert their anti-inflammatory effects on the vascular wall through a variety of molecular pathways of the innate and adaptive immune systems, their impact on the circulating levels of pro-inflammatory cytokines, and their effect on adhesion molecules. By inhibiting the mevalonate pathway and isoprenoid formation, statins account for the increase of nitric oxide bioavailability and the improvement of vascular and myocardial redox state by multiple different mechanisms (directly or indirectly through low-density lipoprotein [LDL] lowering). A large number of randomized control trials have shown that statins help in the primary and secondary prevention of cardiovascular events, not only via their lipid-lowering effect, but also due to their anti-inflammatory potential as well. In this paper, we examine the molecular pathways in which statins are implicated and exert their anti-inflammatory effects, and we focus specifically on their impact on innate and adaptive immunity systems. Finally, we review the most important clinical data for the role of statins in primary and secondary prevention of cardiovascular events
Role of human epicardial adipose tissue–derived miR-92a-3p in myocardial redox state
Background
Visceral obesity is directly linked to increased cardiovascular risk, including heart failure.
Objectives
This study explored the ability of human epicardial adipose tissue (EAT)-derived microRNAs (miRNAs) to regulate the myocardial redox state and clinical outcomes.
Methods
This study screened for miRNAs expressed and released from human EAT and tested for correlations with the redox state in the adjacent myocardium in paired EAT/atrial biopsy specimens from patients undergoing cardiac surgery. Three miRNAs were then tested for causality in an in vitro model of cardiomyocytes. At a clinical level, causality/directionality were tested using genome-wide association screening, and the underlying mechanisms were explored using human biopsy specimens, as well as overexpression of the candidate miRNAs and their targets in vitro and in vivo using a transgenic mouse model. The final prognostic value of the discovered targets was tested in patients undergoing cardiac surgery, followed up for a median of 8 years.
Results
EAT miR-92a-3p was related to lower oxidative stress in human myocardium, a finding confirmed by using genetic regulators of miR-92a-3p in the human heart and EAT. miR-92a-3p reduced nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase–derived superoxide (O2.–) by targeting myocardial expression of WNT5A, which regulated Rac1-dependent activation of NADPH oxidases. Finally, high miR-92a-3p levels in EAT were independently related with lower risk of adverse cardiovascular events.
Conclusions
EAT-derived miRNAs exert paracrine effects on the human heart. Indeed miR-92a-3p suppresses the wingless-type MMTV integration site family, member 5a/Rac1/NADPH oxidase axis and improves the myocardial redox state. EAT-derived miR-92a-3p is related to improved clinical outcomes and is a rational therapeutic target for the prevention and treatment of obesity-related heart disease
Statins as Pleiotropic Modifiers of Vascular Oxidative Stress and Inflammation
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the industrialized world and in the future is expected to be the number one killer worldwide. The main cause underlying CVD is atherosclerosis. A key event in atherosclerosis initiation and progression is oxidative stress through the production of reactive oxygen species as well as endothelial dysfunction. Several pro- inflammatory and anti-inflammatory cytokines and proteins are involved in this process, complemented by activation of adhesion molecules that promote leukocyte rolling, tethering and infiltration into the sub-endothelial space. Statins represent the agent of choice since numerous clinical trials have verified that their pharmacological action extends beyond lipid lowering. Statins demonstrate direct anti-oxidant effects by scavenging free radicals and stimulating anti-oxidant enzymes while acting as regulators for cytokine, protein and adhesion molecule expression, all of which are involved in the atherosclerotic process. Statin use is considered one of the most efficient currently used interventions in managing CVD with the likely hood of remaining so in the near future
Statins as Pleiotropic Modifiers of Vascular Oxidative Stress and Inflammation.
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the industrialized world and in the future is expected to be the number one killer worldwide. The main cause underlying CVD is atherosclerosis. A key event in atherosclerosis initiation and progression is oxidative stress through the production of reactive oxygen species as well as endothelial dysfunction. Several pro- inflammatory and anti-inflammatory cytokines and proteins are involved in this process, complemented by activation of adhesion molecules that promote leukocyte rolling, tethering and infiltration into the sub-endothelial space. Statins represent the agent of choice since numerous clinical trials have verified that their pharmacological action extends beyond lipid lowering. Statins demonstrate direct anti-oxidant effects by scavenging free radicals and stimulating anti-oxidant enzymes while acting as regulators for cytokine, protein and adhesion molecule expression, all of which are involved in the atherosclerotic process. Statin use is considered one of the most efficient currently used interventions in managing CVD with the likely hood of remaining so in the near future
Dosage Effects of an 810 nm Diode Laser on the Proliferation and Growth Factor Expression of Human Gingival Fibroblasts: Dose Effects of an 810 nm Diode on Gingival Fibroblasts
Introduction: A substantial amount of evidence supports the positive effect of photobiomodulation on the proliferation and differentiation of various cell types. Several laser wavelengths have been used for wound healing improvement, and their actual outcome depends on the settings utilized during irradiation. However, the heterogeneous wavelengths and laser settings applied in the existing literature make it difficult to draw solid conclusions and comparison of different studies. The aim of the present study is to evaluate and compare the effects of various doses of laser energy, provided by an 810 nm diode, on human gingival fibroblasts in terms of proliferation and expression of growth factors with a pivotal role in wound healing.Methods: Human gingival fibroblasts were cultured on plastic tissue culture and irradiated with 2, 4, 6 or 12 J/cm2. The effects of the low-level laser therapy (LLLT) using an 810 nm diode laser on growth factor expression (EGF, TGF and VEGF) were evaluated by qPCR at 72 hours and 7 days after irradiation. Cell proliferation was evaluated at 24, 48 and 72 hours after LLLT using MTT assay.Results: Energy density of 12 J/cm2 provoked irradiated gingival fibroblasts to demonstrate significantly higher proliferation as well as higher gene expression of Col1, VEGF and EGF. LLLT positive effects were obvious up to 7 days post-irradiation.Conclusion: LLLT with 810 nm presents beneficial effects on proliferation, collagen production and growth factor expression in human gingival fibroblast cells. The application of 12 J/cm2 can be suggested as the optimal energy density for the enhancement of the wound healing process.
DOI: 10.34172/jlms.2021.2
Innate and Adaptive Inflammation as a Therapeutic Target in Vascular Disease
Atherosclerosis, the main pathophysiological condition leading to
cardiovascular disease (CVD), is now considered to be a chronic
inflammatory condition. Statins are the most widely used and promising
agents in treating CVD and are renowned for their pleiotropic
lipid-lowering independent effects. Statins exert their
anti-inflammatory effects on the vascular wall through a variety of
molecular pathways of the innate and adaptive immune systems, their
impact on the circulating levels of pro-inflammatory cytokines, and
their effect on adhesion molecules. By inhibiting the mevalonate pathway
and isoprenoid formation, statins account for the increase of nitric
oxide bioavailability and the improvement of vascular and myocardial
redox state by multiple different mechanisms (directly or indirectly
through low-density lipoprotein [LDL] lowering). A large number of
randomized control trials have shown that statins help in the primary
and secondary prevention of cardiovascular events, not only via their
lipid-lowering effect, but also due to their anti-inflammatory potential
as well. In this paper, we examine the molecular pathways in which
statins are implicated and exert their anti-inflammatory effects, and we
focus specifically on their impact on innate and adaptive immunity
systems. Finally, we review the most important clinical data for the
role of statins in primary and secondary prevention of cardiovascular
events. (c) 2014 by the American College of Cardiology Foundatio
Nd:YAG laser radiation (1.064 nm) accelerates differentiation of osteoblasts to osteocytes on smooth and rough titanium surfaces in vitro
BACKGROUND: A number of studies revealed beneficial effects of low-level laser therapy (LLLT) regarding cell proliferation and differentiation.
AIM: To investigate the effect of Nd:YAG (1.064 nm) laser radiation in the proliferation and differentiation potential of MG-63 osteoblast-like cells. Additionally, the effects of the surface configurations were to be evaluated.
MATERIAL AND METHODS: MG-63 osteoblast cells were cultured on different surfaces: plastic tissue culture, smooth (polished) titanium-PT and rough titanium-SLA. The effects of both titanium surfaces and low-level laser therapy (LLLT) on cell adhesion were evaluated by the gene expression of molecules involved in cell proliferation and differentiation. In addition, scanning electron microscopy (SEM) and MTT proliferation assays were used to examine cell morphology and proliferation, respectively.
RESULTS: Compared to smooth (PT) surfaces, SLA surfaces favoured MG-63 cell differentiation. Following the application of Nd:YAG laser irradiation, cells yielded statistically significantly improved differentiation on both smooth and SLA surfaces compared with non-irradiated surfaces.
CONCLUSIONS: The findings of this present study suggest that both surface morphology and Nd:YAG laser irradiation influence the proliferation and differentiation potential of MG-63 cells