Insights in Lipids in Cardiovascular Disease: 2021

Editorial

15 July 2022

Editorial: Insights in lipids in cardiovascular disease: 2021

Irena Levitan

and

Tomas Vaisar

1,585 views

0 citations

Editors

Irena Levitan

University of Illinois Chicago

Tomas Vaisar

University of Washington

Impact

Mechanisms of atherosclerosis induced by sdLDL-C. (A) Lipid metabolism: SdLDL-C reduces the expression of ATF3 and EGR2, ATF3 decreases the ability of SR-BI by interacting with p53 and 4α and promotes CYP8B1 to inhibit cholesterol reverse transport; EGR2 leads to an increase in CE production and FC outflow, thus increasing the oxidation sensitivity of sdLDL-C. On the other hand, the low affinity of apoB-100 on the surface of LDL-C receptors and sdLDL-C makes it difficult for the receptors to recognize sdLDL-C and is more easily absorbed by phagocytes to form foam cells and promote the occurrence and development of AS. (B) Oxidative stress: The increase of sdLDL-C level reduces the production of VLCFA and miR-126, which affects lipid metabolism and fatty acid β oxidation; miR-126 affects HDL uptake, and enhances signal transduction resulting in AS. In addition, ox-sdLDL can also increase the expression of adhesion molecules and induce excessive production of ROS and RNS, resulting in the enhancement of oxidative stress to cause AS. (C) Fibrinolytic system: SdLDL-C increases the levels of PAI-1 and TXA2. PAI-1 inhibits the function of u-PA and t-PA, which easily leads to thrombosis. TXA2 activates TP receptor and activates RhoA/Rho21 kinase pathway through its G protein coupled receptor, and increases calcium levels in hepatic stellate cells, resulting in vasoconstriction, platelet aggregation, thrombosis and AS. (D) Inflammation: SdLDL-C levels reduces IDO, causing a decrease in vascular tolerance by affecting the Kyn pathway; LP-PLA2 increased that activated TRPC1/TRPC3 channels, calcium influx, Bax and caspase-3 pathways to cause apoptosis; increased expression of inflammatory cytokines and the formation of foam cell, suggesting an inflammatory response. SdLDL-C, small, dense low-density lipoprotein cholesterol; AS, atherosclerosis; CE, cholesterol ester; FC, free cholesterol; VLCFA, very-long-chain fatty acid; ATF3, activating transcription factor 3; LDs, lipid droplets; IDO, indoleamine 2,3-dioxygenase; LP-PLA2, lipoprotein-associated phospholipase A2; LPCs, lysophosphatidylcholine; ROS, reactive oxygen species; RNS, reactive nitrogen species; PAI-1, plasminogen activator inhibitor 1; TXA2, thromboxane A2; t-PA, tissue type plasminogen activator; u-PA, urokinase type plasminogen activator.

Review

10 February 2022

Small, Dense Low-Density Lipoprotein-Cholesterol and Atherosclerosis: Relationship and Therapeutic Strategies

Xiao Jin

, 2 more and

Min Wu

17,382 views

45 citations

Review

08 March 2022

HDL Composition, Heart Failure, and Its Comorbidities

Ahmed Diab

, 2 more and

Ali Javaheri

5,821 views

15 citations

Boxplots of Lipoprotein(a) levels according to PE severity (n = 811). PE, Pulmonary embolism; LR, Low-risk PE; IML, Intermediate-Low-risk PE; IMH, Intermediate-High-risk PE; HR, High-risk PE.

Brief Research Report

07 February 2022

Lipoprotein(a) and Pulmonary Embolism Severity-A Retrospective Data Analysis

Paul Gressenberger

, 11 more and

Thomas Gary

2,984 views

4 citations

Perspective

06 May 2022

Targeting Lipid—Ion Channel Interactions in Cardiovascular Disease

Emma C. Hudgins

, 2 more and

Ibra S. Fancher

2,762 views

2 citations

Original Research

04 February 2022

High Plasma Concentration of Apolipoprotein C-III Confers an Increased Risk of Cerebral Ischemic Events on Cardiovascular Patients Anticoagulated With Warfarin

Oliviero Olivieri

, 8 more and

Nicola Martinelli

1,983 views

2 citations

Systematic Review

13 December 2021

Cholesterol Efflux Capacity and Its Association With Adverse Cardiovascular Events: A Systematic Review and Meta-Analysis

Jane J. Lee

, 10 more and

C. Michael Gibson

Background: Serum high-density lipoprotein cholesterol (HDL-C) levels are inversely associated with cardiovascular disease events. Yet, emerging evidence suggests that it is the functional properties of HDL, in particular, reverse cholesterol transport, which is a key protective mechanism mediating cholesterol removal from macrophage cells and reducing plaque lipid content. Cholesterol efflux capacity (CEC) measures the capacity of HDL to perform this function. A systematic review and meta-analysis were conducted to explore the association of CEC and adverse cardiovascular events.

Methods: A comprehensive literature review of Embase, PubMed, and Web of Science Core Collection from inception to September 2019 was performed for all studies that examined the association between CEC and cardiovascular outcomes. The primary outcome was adverse cardiovascular events, which were inclusive of atherosclerotic cardiovascular disease (ASCVD) or mortality.

Results: A total of 20 trials were included. Compared with low CEC levels, high CEC levels were associated with a 37% lower risk of adverse cardiovascular events (crude RR = 0.63; 95% CI, 0.52–0.76; P < 0.00001). Every SD increase of CEC was associated with a 20% lower risk of adverse cardiovascular events (HR = 0.80; 95% CI, 0.66–0.97; P = 0.02). The association remained significant after adjusting for cardiovascular risk factors, medications, and HDL-C levels (HR = 0.76; 95% CI, 0.63–0.91; P = 0.004). A significant CEC-endpoint relationship was observed (P = 0.024) such that for every 0.1 unit increase in CEC, there was a 5% reduced risk for adverse cardiovascular events (RR = 0.95; 95% CI, 0.91–0.99).

Conclusions: Higher CEC is associated with lower adverse cardiovascular outcomes. These findings warrant further research on whether CEC is merely a biomarker or a mechanism that could be targeted as a pharmacologic intervention for improving clinical outcomes.

PROSPERO Registration Number: CRD42020146681; https://www.crd.york.ac.uk/prospero/.

5,332 views

43 citations