CD36 restricts lipid-associated macrophages accumulation in white adipose tissues during atherogenesis.

Visceral white adipose tissues (WAT) regulate systemic lipid metabolism and inflammation. Dysfunctional WAT drive chronic inflammation and facilitate atherosclerosis. Adipose tissue-associated macrophages (ATM) are the predominant immune cells in WAT, but their heterogeneity and phenotypes are poorly defined during atherogenesis.

Distinguishing ASH clinical practice guidelines from other forms of ASH clinical advice.

The American Society of Hematology (ASH) develops a variety of resources that provide guidance to clinicians on the diagnosis and management of blood diseases. These resources include clinical practice guidelines (CPGs) and other forms of clinical advice. Although both ASH CPGs and other forms of clinical advice provide recommendations, they differ with respect to the methods underpinning their development, the principal type of recommendations they offer, their transparency and concordance with published evidence, and the time and resources required for their development.

Targeting Cysteine Oxidation in Thrombotic Disorders.

Oxidative stress increases the risk for clinically significant thrombotic events, yet the mechanisms by which oxidants become prothrombotic are unclear. In this review, we provide an overview of cysteine reactivity and oxidation. We then highlight recent findings on cysteine oxidation events in oxidative stress-related thrombosis.

Plasma tissue-type plasminogen activator is associated with lipoprotein(a) and clinical outcomes in hospitalized patients with COVID-19.

Background: Patients with COVID-19 have a higher risk of thrombosis and thromboembolism, but the underlying mechanism(s) remain to be fully elucidated. In patients with COVID-19, high lipoprotein(a) (Lp(a)) is positively associated with the risk of ischemic heart disease. Lp(a), composed of an apoB-containing particle and apolipoprotein(a) (apo(a)), inhibits the key fibrinolytic enzyme, tissue-type plasminogen activator (tPA).

Intracellular tPA-PAI-1 interaction determines VLDL assembly in hepatocytes.

Apolipoprotein B (apoB)-lipoproteins initiate and promote atherosclerotic cardiovascular disease. Plasma tissue plasminogen activator (tPA) activity is negatively associated with atherogenic apoB-lipoprotein cholesterol levels in humans, but the mechanisms are unknown. We found that tPA, partially through the lysine-binding site on its Kringle 2 domain, binds to the N terminus of apoB, blocking the interaction between apoB and microsomal triglyceride transfer protein (MTP) in hepatocytes, thereby reducing very-low-density lipoprotein (VLDL) assembly and plasma apoB-lipoprotein cholesterol levels.

Contribution of adipocyte Na/K-ATPase α1/CD36 signaling induced exosome secretion in response to oxidized LDL.

Introduction: Adipose tissue constantly secretes adipokines and extracellular vesicles including exosomes to crosstalk with distinct tissues and organs for whole-body homeostasis. However, dysfunctional adipose tissue under chronic inflammatory conditions such as obesity, atherosclerosis, and diabetes shows pro-inflammatory phenotypes accompanied by oxidative stress and abnormal secretion. Nevertheless, molecular mechanisms of how adipocytes are stimulated to secrete exosomes under those conditions remain poorly understood.

The correlations among racial/ethnic groups, hypertriglyceridemia, thrombosis, and mortality in hospitalized patients with COVID-19.

Reports of racial and ethnic disparities regarding both rates of infection of the SARS-CoV-2 virus and morbidity of the coronavirus disease-19 (COVID-19) contain profound differences depending on the population. Our previous study has shown that patients with COVID-19 who developed hypertriglyceridemia during hospitalization have a 2.3 times higher mortality rate.

A CD36 transmembrane domain peptide interrupts CD36 interactions with membrane partners on macrophages and inhibits atherogenic functions.

CD36 is a transmembrane glycoprotein receptor for oxidized low density lipoprotein (LDL) and other endogenous danger signals and promotes athero-thrombotic processes. CD36 has been shown to associate physically with other transmembrane proteins, including integrins, tetraspanins, and toll-like receptors, which modulate CD36-mediated cell signaling. The CD36 N-terminal transmembrane domain (nTMD) contains a GXXXG sequence motif that mediates protein-protein interactions in many membrane proteins.

Na/K-ATPase suppresses LPS-induced pro-inflammatory signaling through Lyn.

Na/K-ATPase (NKA), besides its ion transporter function, is a signal transducer by regulating Src family kinases (SFK). The signaling NKA contributes to oxidized LDL-induced macrophage foam cell formation and interacts with TLR4. However, its role in lipopolysaccharides (LPS)-induced signaling and glycolytic switch in macrophages remains unclear.

Plasma Membrane Localization of CD36 Requires Vimentin Phosphorylation; A Mechanism by Which Macrophage Vimentin Promotes Atherosclerosis.

Vimentin is a type III intermediate filament protein expressed in cells of mesenchymal origin. Vimentin has been thought to function mainly as a structural protein and roles of vimentin in other cellular processes have not been extensively studied. Our current study aims to reveal functions of vimentin in macrophage foam cell formation, the critical stage of atherosclerosis.

CD36, a signaling receptor and fatty acid transporter that regulates immune cell metabolism and fate.

CD36 is a type 2 cell surface scavenger receptor widely expressed in many immune and non-immune cells. It functions as both a signaling receptor responding to DAMPs and PAMPs, as well as a long chain free fatty acid transporter. Recent studies have indicated that CD36 can integrate cell signaling and metabolic pathways through its dual functions and thereby influence immune cell differentiation and activation, and ultimately help determine cell fate.

Hypertriglyceridemia during hospitalization independently associates with mortality in patients with COVID-19.

Background: Alteration in blood triglyceride levels have been found in patients with coronavirus disease 2019 (COVID-19). However, the association between hypertriglyceridemia and mortality in COVID-19 patients is unknown.

Objective: To investigate the association between alteration in triglyceride level and mortality in hospitalized COVID-19 patients.

AMPK-deficiency forces metformin-challenged cancer cells to switch from carbohydrate metabolism to ketogenesis to support energy metabolism.

Epidemiologic studies in diabetic patients as well as research in model organisms have indicated the potential of metformin as a drug candidate for the treatment of various types of cancer, including breast cancer. To date most of the anti-cancer properties of metformin have, in large part, been attributed either to the inhibition of mitochondrial NADH oxidase complex (Complex I in the electron transport chain) or the activation of AMP-activated kinase (AMPK). However, it is becoming increasingly clear that AMPK activation may be critical to alleviate metabolic and energetic stresses associated with tumor progression suggesting that it may, in fact, attenuate the toxicity of metformin instead of promoting it.

Development of an arteriolar niche and self-renewal of breast cancer stem cells by lysophosphatidic acid/protein kinase D signaling.

Breast cancer stem cells (BCSCs) are essential for cancer growth, metastasis and recurrence. The regulatory mechanisms of BCSC interactions with the vascular niche within the tumor microenvironment (TME) and their self-renewal are currently under extensive investigation. We have demonstrated the existence of an arteriolar niche in the TME of human BC tissues.

Details of developing and implementing an intensive interdisciplinary care program for high need, high cost patients.

1. Developing and implementing an intensive interdisciplinary medical home within a large academic medical center was feasible. 2.

Targeting PIM1-Mediated Metabolism in Myeloid Suppressor Cells to Treat Cancer.

There is a strong correlation between myeloid-derived suppressor cells (MDSC) and resistance to immune checkpoint blockade (ICB), but the detailed mechanisms underlying this correlation are largely unknown. Using single-cell RNA sequencing analysis in a bilateral tumor model, we found that immunosuppressive myeloid cells with characteristics of fatty acid oxidative metabolism dominate the immune-cell landscape in ICB-resistant subjects. In addition, we uncovered a previously underappreciated role of a serine/threonine kinase, PIM1, in regulating lipid oxidative metabolism via PPARγ-mediated activities.

Cysteine sulfenylation by CD36 signaling promotes arterial thrombosis in dyslipidemia.

Arterial thrombosis in the setting of dyslipidemia promotes clinically significant events, including myocardial infarction and stroke. Oxidized lipids in low-density lipoproteins (oxLDL) are a risk factor for athero-thrombosis and are recognized by platelet scavenger receptor CD36. oxLDL binding to CD36 promotes platelet activation and thrombosis by promoting generation of reactive oxygen species.

Oxidant-Induced Alterations in the Adipocyte Transcriptome: Role of the Na,K-ATPase Oxidant Amplification Loop.

(1) Background: Recently we have noted that adipocyte specific expression of the peptide, NaKtide, which was developed to attenuate the Na,K-ATPase oxidant amplification loop, could ameliorate the phenotypical features of uremic cardiomyopathy. We performed this study to better characterize the cellular transcriptomes that are involved in various biological pathways associated with adipocyte function occurring with renal failure. (2) Methods: RNAseq was performed on the visceral adipose tissue of animals subjected to partial nephrectomy.

CD36-mediated metabolic adaptation supports regulatory T cell survival and function in tumors.

Depleting regulatory T cells (T cells) to counteract immunosuppressive features of the tumor microenvironment (TME) is an attractive strategy for cancer treatment; however, autoimmunity due to systemic impairment of their suppressive function limits its therapeutic potential. Elucidating approaches that specifically disrupt intratumoral T cells is direly needed for cancer immunotherapy. We found that CD36 was selectively upregulated in intrautumoral T cells as a central metabolic modulator.

Modification of HDL by reactive aldehydes alters select cardioprotective functions of HDL in macrophages.

While increased levels of high-density lipoprotein (HDL)-cholesterol correlate with protection against cardiovascular disease, recent findings demonstrate that HDL function, rather than HDL-cholesterol levels, may be a better indicator of cardiovascular risk. One mechanism by which HDL function can be compromised is through modification by reactive aldehydes such as acrolein (Acro), 4-hydroxynonenal, and malondialdehyde (MDA). In this study, we tested the hypothesis that modification of HDL with reactive aldehydes would impair HDL's athero-protective functions in macrophages.

CD36 and ERK5 link dyslipidemia to apoptotic-like platelet procoagulant function.

Purpose Of Review: Metabolic diseases, including dyslipidemia, diabetes mellitus, and chronic inflammation are risk factors for clinically significant thrombotic events. Thrombosis in these settings is multifaceted with coordinated mechanisms between platelet activation and the hemostatic pathways. This review focuses on recent advances in platelet procoagulant and apoptotic signaling with emphasis on the pathophysiologic mechanisms induced by platelet CD36 in dyslipidemia, and the key unaddressed questions relating to the field.