Proprotein convertase subtilisin/kexin type 9 inhibitors and lipoprotein(a)-mediated risk of atherosclerotic cardiovascular disease: more than meets the eye?
Purpose of review
Evidence continues to mount for elevated lipoprotein(a) [Lp(a)] as a prevalent, independent, and causal risk factor for atherosclerotic cardiovascular disease. However, the effects of existing lipid-lowering therapies on Lp(a) are comparatively modest and are not specific to Lp(a). Consequently, evidence that Lp(a)-lowering confers a cardiovascular benefit is lacking. Large-scale cardiovascular outcome trials (CVOTs) of inhibitory mAbs targeting proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) may address this issue.
Recent findings
Although the ability of PCSK9i to lower Lp(a) by 15...
Source: Current Opinion in Lipidology - November 5, 2019 Category: Lipidology Tags: THERAPY AND CLINICAL TRIALS: Edited by Erik S.G. Stroes and Gerald F. Watts Source Type: research
SPPARM alpha: the Lazarus effect
Purpose of review
Atherogenic dyslipidaemia, characterized by high plasma triglycerides (a surrogate for triglyceride-rich remnant lipoproteins) and low high-density lipoprotein cholesterol (HDL-C), is prevalent in patients with type 2 diabetes mellitus (T2DM) and contributes to a high modifiable residual cardiovascular risk. Fibrates are effective in managing hypertriglyceridaemia but lack consistent cardiovascular benefit in clinical trials and exhibit pharmacokinetic interaction with statins (gemfibrozil) and renal and hepatic safety issues (fenofibrate). The selective peroxisome proliferator-activated receptor alpha ...
Source: Current Opinion in Lipidology - November 5, 2019 Category: Lipidology Tags: THERAPY AND CLINICAL TRIALS: Edited by Erik S.G. Stroes and Gerald F. Watts Source Type: research
Editorial: New targets, treatments and trials for preventing and reversing atherosclerosis: the paradox of choice
No abstract available (Source: Current Opinion in Lipidology)
Source: Current Opinion in Lipidology - November 5, 2019 Category: Lipidology Tags: THERAPY AND CLINICAL TRIALS: Edited by Erik S.G. Stroes and Gerald F. Watts Source Type: research
Editorial introductions
No abstract available (Source: Current Opinion in Lipidology)
Source: Current Opinion in Lipidology - November 5, 2019 Category: Lipidology Tags: EDITORIAL INTRODUCTIONS Source Type: research
Update on genetics and molecular biology
No abstract available (Source: Current Opinion in Lipidology)
Source: Current Opinion in Lipidology - September 4, 2019 Category: Lipidology Tags: BIMONTHLY UPDATE: Edited by Alan Rees Source Type: research
Diet and cognitive decline: considerations for reconciling heterogeneous findings
No abstract available (Source: Current Opinion in Lipidology)
Source: Current Opinion in Lipidology - September 4, 2019 Category: Lipidology Tags: BIMONTHLY UPDATE: Edited by Alan Rees Source Type: research
Links lipoproteins to chronic kidney disease and atherosclerosis
No abstract available (Source: Current Opinion in Lipidology)
Source: Current Opinion in Lipidology - September 4, 2019 Category: Lipidology Tags: BIMONTHLY UPDATE: Edited by Alan Rees Source Type: research
Monocytes and macrophages in atherogenesis
Purpose of review
Monocytes and macrophages are key players in the pathogenesis of atherosclerosis and dictate atherogenesis growth and stability. The heterogeneous nature of myeloid cells concerning their metabolic and phenotypic function is increasingly appreciated. This review summarizes the recent monocyte and macrophage literature and highlights how differing subsets contribute to atherogenesis.
Recent findings
Monocytes are short-lived cells generated in the bone marrow and released to circulation where they can produce inflammatory cytokines and, importantly, differentiate into long-lived macrophages. In the co...
Source: Current Opinion in Lipidology - September 4, 2019 Category: Lipidology Tags: ATHEROSCLEROSIS: CELL BIOLOGY AND LIPOPROTEINS: Edited by Mohamad Navab and Menno de Winther Source Type: research
Trained immunity and atherosclerotic cardiovascular disease
Purpose of review
The two major challenges in cardiovascular medicine are to refine risk prediction and to improve pharmacological prevention and treatment. The concept of innate immune memory, which is called trained immunity, has the potential to improve clinical practice in these regards.
Recent findings
Monocytes and macrophages have the capability to develop a long-term proinflammatory and proatherogenic phenotype after brief exposure to inflammatory stimuli, such as oxidized low-density lipoprotein particles. This innate immune memory develops because of rewiring of intracellular metabolic pathways and epigeneti...
Source: Current Opinion in Lipidology - September 4, 2019 Category: Lipidology Tags: ATHEROSCLEROSIS: CELL BIOLOGY AND LIPOPROTEINS: Edited by Mohamad Navab and Menno de Winther Source Type: research
Maximizing the benefits of cholesterol-lowering drugs
Purpose of review
Drugs to lower LDL-C levels are very widely used. In this brief review, I will use selected recent studies to delineate several important principles that provide a rationale for how to maximize the benefits of using LDL-C lowering drugs to reduce cardiovascular disease. The focus will be on using statins, ezetimibe, and PCSK9 monoclonal antibodies as recent studies have predominantly utilized these agents.
Recent findings
The key principles to consider when using LDL-C-lowering drugs to reduce cardiovascular disease are: the lower the LDL-C the better; the sooner and the longer one lowers LDL-C the b...
Source: Current Opinion in Lipidology - September 4, 2019 Category: Lipidology Tags: ATHEROSCLEROSIS: CELL BIOLOGY AND LIPOPROTEINS: Edited by Mohamad Navab and Menno de Winther Source Type: research
The role of the small intestine in modulating metabolism and inflammation in atherosclerosis and cancer
Purpose of review
To discuss recent findings on the importance of the small intestine in modulating metabolism and inflammation in atherosclerosis and cancer.
Recent findings
Integrin β7+ natural gut intraepithelial T cells modulated metabolism and accelerated atherosclerosis in mice. Reducing the generation of lysophospholipids in the small intestine mimicked bariatric surgery and improved diabetes. Enterocyte-specific knockdown of stearoyl-CoA desaturase-1 significantly improved dyslipidemia in LDL receptor null (Ldlr−/−) mice fed a Western diet. Adding a concentrate of tomatoes transgenic for the apolipoprotei...
Source: Current Opinion in Lipidology - September 4, 2019 Category: Lipidology Tags: ATHEROSCLEROSIS: CELL BIOLOGY AND LIPOPROTEINS: Edited by Mohamad Navab and Menno de Winther Source Type: research
Neointimal hyperplasia: are fatty acid transport proteins a new therapeutic target?
Purpose of review
High-fat diets contribute to hyperlipidemia and dysregulated metabolism underlying insulin resistant states and cardiovascular diseases. Neointimal hyperplasia is a significant resulting morbidity. Increased fatty acid (FA) levels lead to dysfunctional endothelium, defined as activated, proinflammatory and prothrombotic. The purpose of this review is to assess the recent literature on the emerging concept that uptake of FA into many tissues is regulated at the endothelial level, and this in turn contributes to endothelial dysfunction, an initiating factor in insulin resistant states, atherosclerosis and...
Source: Current Opinion in Lipidology - September 4, 2019 Category: Lipidology Tags: ATHEROSCLEROSIS: CELL BIOLOGY AND LIPOPROTEINS: Edited by Mohamad Navab and Menno de Winther Source Type: research
Intestinal lymphatic vessels and their role in chylomicron absorption and lipid homeostasis
Purpose of review
In this review, we describe novel findings related to intestinal lipid transport in lymphatic vessels.
Recent findings
Studies have shown that chylomicron entry to lacteals and lymph movement in intestinal lymphatic capillaries is an active process. Regulators of this intestinal chylomicron transport include among others the autonomous nervous system, transcription factors like PLAGL2, and molecular regulators, such as VEGF-A/Nrp1/VEGFR1, VEGF-C/VEGFR3, DLL4, CALCRL and GLP-2. Chylomicron transport in intestinal lymphatics is now emerging not only as an option for drug delivery but also as a new cand...
Source: Current Opinion in Lipidology - September 4, 2019 Category: Lipidology Tags: ATHEROSCLEROSIS: CELL BIOLOGY AND LIPOPROTEINS: Edited by Mohamad Navab and Menno de Winther Source Type: research
Triglycerides and endothelial function: molecular biology to clinical perspective
Purpose of review
Recently, a high level of triglycerides has attracted much attention as an important residual risk factor of cardiovascular events. We will review and show the mechanisms underlying the association of endothelial dysfunction with hypertriglyceridemia and present clinical evidence for a relationship between endothelial function and triglycerides.
Recent findings
Clinical studies have shown that hypertriglyceridemia is associated with endothelial dysfunction. It is likely that hypertriglyceridemia impairs endothelial function through direct and indirect mechanisms. Therefore, hypertriglyceridemia is re...
Source: Current Opinion in Lipidology - September 4, 2019 Category: Lipidology Tags: ATHEROSCLEROSIS: CELL BIOLOGY AND LIPOPROTEINS: Edited by Mohamad Navab and Menno de Winther Source Type: research
Regulation of calcific vascular and valvular disease by nuclear receptors
Purpose of review
This review addresses recent developments in studies of lipid regulation of calcific disease of arteries and cardiac valves, including the role of nuclear receptors. The role of lipid-soluble signals and their receptors is timely given the recent evidence and concerns that lipid-lowering treatment may increase the rate of progression of coronary artery calcification, which has been long associated with increased cardiovascular risk. Understanding the mechanisms will be important for interpreting such clinical information.
Recent findings
New findings support regulation of calcific vascular and valvul...
Source: Current Opinion in Lipidology - September 4, 2019 Category: Lipidology Tags: ATHEROSCLEROSIS: CELL BIOLOGY AND LIPOPROTEINS: Edited by Mohamad Navab and Menno de Winther Source Type: research
