From Lipids to Inflammation

Shapiro, Michael D.; Fazio, Sergio

doi:10.1161/circresaha.115.306471

Cited by 182 publications

(80 citation statements)

References 186 publications

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“…The non-pleiotropic GRS for IHD excluded SNPs associated with lipids and mainly reflects inmuno-inflammatory mechanisms. Therefore, this interaction could be explained by the independent interrelationships between lipids and inmuno-inflammation that could trigger the deleterious consequences of these two factors through different mechanisms 38,39 .…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular Risk Factors and Ischemic Heart Disease

Elosúa

Lluís-Ganella

Subirana

et al. 2016

Circ Cardiovasc Genet

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Background Cardiovascular risk factors tend to aggregate. The biological and predictive value of this aggregation is questioned and genetics could shed light on this debate. Our aim was to reappraise the impact of risk factor confluence on ischemic heart disease (IHD) risk by testing whether genetic risk scores (GRSs) associated with these factors interact on an additive or multiplicative scale, and to determine whether these interactions provide additional value for predicting IHD risk. Methods and Results We selected genetic variants associated with blood pressure, body mass index, waist circumference, triglycerides, type-2 diabetes, HDL and LDL cholesterol, and IHD to create GRSs for each factor. We tested and meta-analyzed the impact of additive (Synergy Index –SI–) and multiplicative (βinteraction) interactions between each GRS pair in one case-control (n=6,042) and four cohort studies (n=17,794), and evaluated the predictive value of these interactions. We observed two multiplicative interactions: GRSLDL·GRSTriglycerides (βinteraction=−0.096; Standard Error=0.028) and non-pleiotropic GRSIHD·GRSLDL (βinteraction=0.091; Standard Error=0.028). Inclusion of these interaction terms did not improve predictive capacity. Conclusions The confluence of LDL cholesterol and triglycerides genetic risk load has an additive effect on IHD risk. The interaction between LDL cholesterol and IHD genetic load is more than multiplicative, supporting the hazardous impact on atherosclerosis progression of the combination of inflammation and increased lipid levels. The capacity of risk factor confluence to improve IHD risk prediction is questionable. Further studies in larger samples are warranted to confirm and expand our results.

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Section: Discussionmentioning

confidence: 99%

Cardiovascular Risk Factors and Ischemic Heart Disease

Elosúa

Lluís-Ganella

Subirana

et al. 2016

Circ Cardiovasc Genet

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“…Elevated plasma levels of low density lipoprotein cholesterol (LDL-C) remain a strong risk factor for atherosclerosis (161, 162). The retention of these particles within the intima of arteries along with the production of ROS, lipid peroxidation products and inflammatory mediators, leads to the development of atherosclerotic plaques (163).…”

Section: Metabolic Homeostasis In Phagocytes Post An Apoptotic Cell Mealmentioning

confidence: 99%

The many ways tissue phagocytes respond to dying cells

Blander

2017

Immunological Reviews

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Summary Apoptosis is an important component of normal tissue physiology, and the prompt removal of apoptotic cells is equally essential to avoid the undesirable consequences of their accumulation and disintegration. Professional phagocytes are highly specialized for engulfing apoptotic cells. The recent ability to track cells that have undergone apoptosis in situ has revealed a division of labor among the tissue resident phagocytes that sample them. Macrophages are uniquely programmed to process internalized apoptotic cell-derived fatty acids, cholesterol and nucleotides, as a reflection of their dominant role in clearing the bulk of apoptotic cells. Dendritic cells carry apoptotic cells to lymph nodes where they signal the emergence and expansion of highly suppressive regulatory CD4 T cells. A broad suppression of inflammation is executed through distinct phagocyte-specific mechanisms. A clever induction of negative regulatory nodes is notable in dendritic cells serving to simultaneously shut down multiple pathways of inflammation. Several of the genes and pathways modulated in phagocytes in response to apoptotic cells have been linked to chronic inflammatory and autoimmune diseases such as atherosclerosis, inflammatory bowel disease and systemic lupus erythematosus. Our collective understanding of old and new phagocyte functions after apoptotic cell phagocytosis demonstrates the enormity of ways to mediate immune suppression and enforce tissue homeostasis.

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“…It is now widely accepted that chronic inflammation plays a causal role in the development of CVD and finding new ways to target the inflammatory response is gaining traction as a new therapeutic approach to treating CVD in conjunction with the current standard of care (e.g., aspirin, statins, anti-platelet therapies) 15 . Unlike traditional anti-inflammatory strategies that blunt the production of inflammation “initiators” and could potentially lead to immunosuppression, pro-resolving mediators resolve inflammation without compromising host-defense 2 .…”

Section: 7 Summary and Future Directionsmentioning

confidence: 99%

“…Specifically, the Cardiovascular Inflammation Reduction Trial (CIRT) is utilizing low dose methotrexate to determine whether blocking inflammation will lower vascular events rates 12, 13 . Similarly, the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) is testing whether an interleukin 1β antibody will decrease chronic vascular inflammation and cardiovascular events without affecting cholesterol levels 14, 15 . While these clinical trials could provide evidence for a causal role of inflammation in atherosclerosis in humans, targeting pro-resolution pathways may offer additional advantages over traditional anti-inflammatory approaches that can be immunosupressive 2 .…”

Section: 1 Introductionmentioning

confidence: 99%

Specialized pro-resolving mediators in cardiovascular diseases

Fredman

Spite

2017

Molecular Aspects of Medicine

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The resolution of inflammation is a highly regulated process enacted by endogenous mediators including specialized pro-resolving lipid mediators (SPMs): the lipoxins, resolvins, protectins and maresins. SPMs activate specific cellular receptors to temper the production of pro-inflammatory mediators, diminish the recruitment of neutrophils, and promote the clearance of dead cells by macrophages. These mediators also enhance host-defense and couple resolution of inflammation to subsequent phases of tissue repair. Given that unresolved inflammation plays a causal role in the development of cardiovascular diseases, an understanding of these endogenous pro-resolving processes is critical for determining why cardiovascular inflammation does not resolve. Here, we discuss the receptor-dependent actions of resolvins and related pro-resolving mediators and highlight their emerging roles in the cardiovascular system. We propose that stimulating resolution could be a novel approach for treating chronic cardiovascular inflammation without promoting immunosuppression.

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From Lipids to Inflammation

Cited by 182 publications

References 186 publications

Cardiovascular Risk Factors and Ischemic Heart Disease

Cardiovascular Risk Factors and Ischemic Heart Disease

The many ways tissue phagocytes respond to dying cells

Specialized pro-resolving mediators in cardiovascular diseases

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