Targeting inflammation in atherosclerosis — from experimental insights to the clinic

Nature Reviews Drug Discovery, Journal Year: 2021, Volume and Issue: 20(8), P. 589 - 610

Published: May 11, 2021

Language: Английский

---

Atherosclerosis: Recent developments

Cell, Journal Year: 2022, Volume and Issue: 185(10), P. 1630 - 1645

Published: May 1, 2022

Atherosclerosis is an inflammatory disease of the large arteries that major cause cardiovascular (CVD) and stroke. Here, we review current understanding molecular, cellular, genetic, environmental contributions to atherosclerosis, from both individual pathway systems perspectives. We place emphasis on recent developments, some which have yielded unexpected biology, including previously unknown heterogeneity smooth muscle cells in atherosclerotic lesions, roles for senescence clonal hematopoiesis, links gut microbiome.

Language: Английский

---

Inflammation and atherosclerosis: signaling pathways and therapeutic intervention

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: April 22, 2022

Atherosclerosis is a chronic inflammatory vascular disease driven by traditional and nontraditional risk factors. Genome-wide association combined with clonal lineage tracing clinical trials have demonstrated that innate adaptive immune responses can promote or quell atherosclerosis. Several signaling pathways, are associated the response, been implicated within atherosclerosis such as NLRP3 inflammasome, toll-like receptors, proprotein convertase subtilisin/kexin type 9, Notch Wnt which of importance for development regression. Targeting especially inflammasome pathway its regulated cytokine interleukin-1β, could represent an attractive new route treatment atherosclerotic diseases. Herein, we summarize knowledge on cellular participants key pathways in atherosclerosis, discuss preclinical studies targeting these going to target some processes, effects quelling inflammation clinic.

Language: Английский

---

How the immune system shapes atherosclerosis: roles of innate and adaptive immunity

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 22(4), P. 251 - 265

Published: Aug. 13, 2021

Language: Английский

---

Vascular smooth muscle cells in atherosclerosis: time for a re-assessment

Cardiovascular Research, Journal Year: 2021, Volume and Issue: 117(11), P. 2326 - 2339

Published: Feb. 5, 2021

Vascular smooth muscle cells (VSMCs) are key participants in both early and late-stage atherosclerosis. VSMCs invade the atherosclerotic lesion from media, expanding lesions, but also forming a protective fibrous cap rich extracellular matrix to cover 'necrotic' core. Hence, have been viewed as plaque-stabilizing, decreased VSMC plaque content-often measured by expression of contractile markers-associated with increased vulnerability. However, emergence lineage-tracing transcriptomic studies has demonstrated that comprise much larger proportion plaques than originally thought, demonstrate multiple different phenotypes vivo, roles might be detrimental. down-regulate markers during atherosclerosis whilst adopting alternative phenotypes, including macrophage-like, foam cell-like, osteochondrogenic-like, myofibroblast-like, mesenchymal stem cell-like. phenotypic switching can studied tissue culture, now deep-core region, markedly affects formation stability. In this review, we describe their presumed cellular paracrine functions, regulatory mechanisms control plasticity, impact on atherogenesis

Language: Английский

---

A single-cell atlas of the normal and malformed human brain vasculature

Science, Journal Year: 2022, Volume and Issue: 375(6584)

Published: Jan. 27, 2022

Cerebrovascular diseases are a leading cause of death and neurologic disability. Further understanding disease mechanisms therapeutic strategies requires deeper knowledge cerebrovascular cells in humans. We profiled transcriptomes 181,388 to define cell atlas the adult human cerebrovasculature, including endothelial molecular signatures with arteriovenous segmentation expanded perivascular diversity. By leveraging this reference, we investigated cellular perturbations brain malformations, which stroke young people, identified pathologic transformations abnormal vascular patterning ontology vascularly derived inflammation. illustrate interplay between immune that contributes hemorrhage catalog opportunities for targeting angiogenic inflammatory programs malformations.

Language: Английский

---

Fate and State of Vascular Smooth Muscle Cells in Atherosclerosis

Circulation, Journal Year: 2021, Volume and Issue: 143(21), P. 2110 - 2116

Published: May 24, 2021

Vascular smooth muscle cells (VSMCs) have long been associated with phenotypic modulation/plasticity or dedifferentiation. Innovative technologies in cell lineage tracing, single-cell RNA sequencing, and human genomics integrated to gain unprecedented insights into the molecular reprogramming of VSMCs other phenotypes experimental clinical atherosclerosis. The current thinking is that an apparently small subset contractile undergoes a fate switch transitional, multipotential can adopt plaque-destabilizing (inflammation, ossification) plaque-stabilizing (collagen matrix deposition) states. Several candidate mediators such VSMC state changes are coming light intriguing implications for understanding coronary artery disease risk development new treatment modalities. Here, we briefly summarize some technical conceptual advancements derived from 2 publications Circulation another Nature Medicine that, collectively, illuminate research directions further explore role atherosclerotic disease.

Language: Английский

---

Six Shades of Vascular Smooth Muscle Cells Illuminated by KLF4 (Krüppel-Like Factor 4)

Arteriosclerosis Thrombosis and Vascular Biology, Journal Year: 2021, Volume and Issue: 41(11), P. 2693 - 2707

Published: Sept. 2, 2021

Multiple layers of vascular smooth muscle cells (vSMCs) are present in blood vessels forming the media vessel wall. vSMCs provide a wall structure, enabling it to contract and relax, thus modulating flow. They also play crucial role development diseases, such as atherosclerosis aortic aneurysm formation. display remarkable high degree plasticity. At present, number different vSMC phenotypes has only partially been characterized. By mapping detail identifying triggers for phenotype switching, relevance disease may be identified. Up until recently, were classified either contractile or dedifferentiated (ie, synthetic). However, single-cell RNA sequencing studies revealed arterial highly diverse. Currently, no consensus exist about phenotypes. Therefore, we reviewed data from relevant studies, total 6 The central type that is mesenchymal-like phenotype. Mesenchymal-like subsequently seem differentiate into fibroblast-like, macrophage-like, osteogenic-like, adipocyte-like vSMCs, which contribute differentially disease. This switching between requires transcription factor KLF4 (Kruppel-like 4). Here, performed an integrated analysis recently identified phenotypes, their associated gene expression profiles, previous knowledge better understand transitions pathology.

Language: Английский

---

How vascular smooth muscle cell phenotype switching contributes to vascular disease

Cell Communication and Signaling, Journal Year: 2022, Volume and Issue: 20(1)

Published: Nov. 21, 2022

Abstract Vascular smooth muscle cells (VSMCs) are the most abundant cell in vessels. Earlier experiments have found that VSMCs possess high plasticity. injury stimulates to switch into a dedifferentiated type, also known as synthetic VSMCs, with migration and proliferation capacity for repairing vascular injury. In recent years, largely owing rapid technological advances single-cell sequencing cell-lineage tracing techniques, multiple phenotypes been uncovered aging, atherosclerosis (AS), aortic aneurysm (AA), etc. These all down-regulate contractile proteins such α-SMA calponin1, obtain specific markers similar cellular functions of osteoblast, fibroblast, macrophage, mesenchymal cells. This highly plastic phenotype transformation is regulated by complex network consisting circulating plasma substances, transcription factors, growth inflammatory non-coding RNAs, integrin family, Notch pathway. review focuses on phenotypic characteristics, molecular profile functional role landscape; mechanism regulating switching; contribution switching AS, AA.

Language: Английский

---

Foam Cells in Atherosclerosis: Novel Insights Into Its Origins, Consequences, and Molecular Mechanisms

Frontiers in Cardiovascular Medicine, Journal Year: 2022, Volume and Issue: 9

Published: April 13, 2022

Foam cells play a vital role in the initiation and development of atherosclerosis. This review aims to summarize novel insights into origins, consequences, molecular mechanisms foam atherosclerotic plaques. are originated from monocytes as well vascular smooth muscle (VSMC), stem/progenitor cells, endothelium cells. Novel technologies including lineage tracing single-cell RNA sequencing (scRNA-seq) have revolutionized our understanding subtypes monocyte- VSMC-derived By using scRNA-seq, three main clusters resident-like, inflammatory, triggering receptor expressed on myeloid cells-2 (Trem2

Language: Английский

---