Cholesterol accumulation impairs HIF-1α-dependent immunometabolic reprogramming of LPS-stimulated macrophages by upregulating the NRF2 pathway.

Lipid accumulation in macrophages (Mφs) is a hallmark of atherosclerosis. Yet, how lipid loading modulates Mφ inflammatory responses remains unclear. We endeavored to gain mechanistic insights into how pre-loading with free cholesterol modulates Mφ metabolism upon LPS-induced TLR4 signaling.

Plasma S1P Orchestrates the Reverse Transendothelial Migration of Aortic Intimal Myeloid Cells in Mice.

Background: Myeloid cells (MCs) reside in the aortic intima at regions predisposed to atherosclerosis. Systemic inflammation triggers reverse transendothelial migration (RTM) of intimal MCs into the arterial blood, which orchestrates a protective immune response that clears intracellular pathogens from the arterial intima. Molecular pathways that regulate RTM remain poorly understood.

Oxidized Low-Density Lipoprotein Accumulation in Macrophages Impairs Lipopolysaccharide-Induced Activation of AKT2, ATP Citrate Lyase, Acetyl-Coenzyme A Production, and Inflammatory Gene H3K27 Acetylation.

The accumulation of lipid and the formation of macrophage foam cells is a hallmark of atherosclerosis, a chronic inflammatory disease. To better understand the role of macrophage lipid accumulation in inflammation during atherogenesis, we studied early molecular events that follow the accumulation of oxidized low-density lipoprotein (oxLDL) in cultured mouse macrophages. We previously showed that oxLDL accumulation downregulates the inflammatory response in conjunction with downregulation of late-phase glycolysis.

Oxidized Low-Density Lipoprotein Accumulation Suppresses Glycolysis and Attenuates the Macrophage Inflammatory Response by Diverting Transcription from the HIF-1α to the Nrf2 Pathway.

Lipid accumulation in macrophages (Mφs) is a hallmark of atherosclerosis, yet how lipid accumulation affects inflammatory responses through rewiring of Mφ metabolism is poorly understood. We modeled lipid accumulation in cultured wild-type mouse thioglycolate-elicited peritoneal Mφs and bone marrow-derived Mφs with conditional (Lyz2-Cre) or complete genetic deficiency of Vhl, Hif1a, Nos2, and Nfe2l2. Transfection studies employed RAW264.

Unveiling the Hidden Landscape of Arterial Diseases at Single-Cell Resolution.

High-resolution single-cell technologies have shed light on the pathogenesis of cardiovascular diseases by enabling the discovery of novel cellular and transcriptomic signatures associated with various conditions, and uncovering new contributions of inflammatory processes, immunity, metabolic stress, and risk factors. We review the information obtained from studies using single-cell technologies in tissues with atherosclerosis and aortic aneurysms. Insights are provided on the biology of endothelial, smooth muscle, and immune cells in the arterial intima and media.

Role of myeloid-derived chemokine CCL5/RANTES at an early stage of atherosclerosis.

One of the hallmarks of atherosclerosis is ongoing accumulation of macrophages in the artery intima beginning at disease onset. Monocyte recruitment contributes to increasing macrophage abundance at early stages of atherosclerosis. Although the chemokine CCL5 (RANTES) has been studied in atherosclerosis, its role in the recruitment of monocytes to early lesions has not been elucidated.

Radiation Impacts Early Atherosclerosis by Suppressing Intimal LDL Accumulation.

Rationale: Bone marrow transplantation (BMT) is used frequently to study the role of hematopoietic cells in atherosclerosis, but aortic arch lesions are smaller in mice after BMT.

Objective: To identify the earliest stage of atherosclerosis inhibited by BMT and elucidate potential mechanisms.

Methods And Results: mice underwent total body γ-irradiation, bone marrow reconstitution, and 6-week recovery.

Mammographic microcalcifications and breast cancer tumorigenesis: a radiologic-pathologic analysis.

Background: Microcalcifications (MCs) are tiny deposits of calcium in breast soft tissue. Approximately 30% of early invasive breast cancers have fine, granular MCs detectable on mammography; however, their significance in breast tumorigenesis is controversial. This study had two objectives: (1) to find associations between mammographic MCs and tumor pathology, and (2) to compare the diagnostic value of mammograms and breast biopsies in identifying malignant MCs.

Current practices and challenges of adjuvant chemotherapy in patients with colorectal cancer.

Colorectal cancer is one of the most commonly diagnosed cancers in men and women in the developed world. Although surgery is the foundation of curative treatment, adjuvant chemotherapy also improves overall and disease-free survival in high-risk stage II and all stage III patients. Research strongly suggests that the timing from surgery to adjuvant chemotherapy is critical, because delays to the start of treatment significantly affect patient outcomes.