New Trends in Vascular Inflammation Research: From Biology to Therapy

Editorial

28 August 2019

Editorial: New Trends in Vascular Inflammation Research: From Biology to Therapy

Masanori Aikawa

Ichiro Manabe

and

Nikolaus Marx

2,694 views

2 citations

Editors

Masanori Aikawa

Brigham and Women's Hospital, Harvard Medical School

Nikolaus Marx

University Hospital RWTH Aachen

Ichiro Manabe

Chiba University

Impact

Morphology of pericytes. (A) Schematic image of pericyte-endothelial cell interaction. (B) Whole-mount immunostaining of mouse embryonic skin with antibodies to pericytes (NG2, red) and endothelial cells (PECAM-1, blue) at embryonic day (E) 15.5. Pericytes are semicircular shape and cover blood vessels. (C) Triple immunostaining of E15.5 mouse embryonic brain with antibodies to pericytes (NG2, red; PDGFRβ, green) and endothelial cells (PECAM-1, blue). Scale bars, 50 μm.

Mini Review

27 June 2018

Tissue Specific Origin, Development, and Pathological Perspectives of Pericytes

Tomoko Yamazaki

and

Yoh-suke Mukouyama

32,511 views

152 citations

Cumulative incidence and hazard ratios of cardiovascular mortality (Left) and all-cause mortality (Right) among CANTOS participants allocated to either placebo or canakinumab according to whether post-randomization on-treatment hsCRP levels were above or below 2 mg/L. Hazard ratios are adjusted for age, sex, smoking status, hypertension, diabetes, body mass index, baseline concentration of hsCRP, and baseline concentration of LDL-C. HR, hazard ratio; CI, confidence interval. Ridker (37).

Mini Review

05 June 2018

Antiinflammatory Therapy in Clinical Care: The CANTOS Trial and Beyond

Aaron W. Aday

and

Paul M. Ridker

17,374 views

85 citations

Metabolic regulation by KLFs in liver and skeletal muscle. Shown are major metabolic pathways regulated by KLFs. In liver, KLF15 enhances gluconeogenesis and amino acid metabolism, but inhibits lipogenesis. KLF2 and KLF6 are involved in the development of steatohepatitis and liver fibrosis. In skeletal muscle, KLF15 regulates amino acid catabolism and fatty acid oxidation. KLF5 is also involved in the regulation of fatty acid oxidation.

Review

11 June 2018

Krüppel-Like Factors in Metabolic Homeostasis and Cardiometabolic Disease

Yumiko Oishi

and

Ichiro Manabe

10,592 views

59 citations

Key molecules involved in innate immunity and atherosclerosis pathogenesis. There are multiple molecules and pathways involved in the progression of atherosclerosis that have also been implicated in atherosclerosis regression. They include: 1. LDL/oxLDL, 2. Chemokines that induce monocyte recruitment into the plaque, 3. HDL, 4. Proliferation, 5. Polarization, 6. Pro-inflammatory mediators, 7. Pro-resolving mediators, 8. Apoptosis and efferocytosis, and 9. Macrophage egress out of the plaque.

Review

11 May 2018

Insights From Pre-Clinical and Clinical Studies on the Role of Innate Inflammation in Atherosclerosis Regression

Karishma Rahman

and

Edward A. Fisher

7,187 views

42 citations

Review

03 August 2018

Dynamic Macrophages: Understanding Mechanisms of Activation as Guide to Therapy for Atherosclerotic Vascular Disease

Julius L. Decano

and

Masanori Aikawa

6,994 views

20 citations

Highlighted lncRNAs from the text are shown along with their targets and biological consequences in response to acute (top) or chronic (bottom) vascular inflammation.

Mini Review

14 March 2018

Long Non-Coding RNAs in Vascular Inflammation

Stefan Haemmig

, 1 more and

Mark W. Feinberg

4,153 views

24 citations

Original Research

16 October 2018

Activation of Toll-Like Receptor 9 Impairs Blood Flow Recovery After Hind-Limb Ischemia

Sachiko Nishimoto

, 10 more and

Masataka Sata

3,375 views

8 citations

Review

22 February 2018

Source of Chronic Inflammation in Aging

Fumihiro Sanada

, 5 more and

Ryuichi Morishita

Aging is a complex process that results from a combination of environmental, genetic, and epigenetic factors. A chronic pro-inflammatory status is a pervasive feature of aging. This chronic low-grade inflammation occurring in the absence of overt infection has been defined as “inflammaging” and represents a significant risk factor for morbidity and mortality in the elderly. The low-grade inflammation persists even after reversing pro-inflammatory stimuli such as LDL cholesterol and the renin–angiotensin system (RAS). Recently, several possible sources of chronic low-grade inflammation observed during aging and age-related diseases have been proposed. Cell senescence and dysregulation of innate immunity is one such mechanism by which persistent prolonged inflammation occurs even after the initial stimulus has been removed. Additionally, the coagulation factor that activates inflammatory signaling beyond its role in the coagulation system has been identified. This signal could be a new source of chronic inflammation and cell senescence. Here, we summarized the factors and cellular pathways/processes that are known to regulate low-grade persistent inflammation in aging and age-related disease.

31,730 views

325 citations

Review

05 March 2018

Vascular Senescence in Cardiovascular and Metabolic Diseases

Goro Katsuumi

, 2 more and

Tohru Minamino

18,448 views

167 citations

Select effector functions of vascular smooth muscle KLFs. KLFs differentially affect VSMC differentiation, proliferation, and inflammation through a multitude of mechanisms. KLF5 and 15 exhibit reciprocal regulation of nuclear factor-κB signaling within VSMCs by binding to cofactors p50 and p300, respectively. KLF5 also promotes proliferation and dedifferentiation by modulating important driver of VSMC dedifferentiation, platelet-derived growth factor-A (PDGF-A), and differentially regulating miR transcription. While KLF4 also promotes dedifferentiation, it resists VSMC proliferation through the transcription of CDKN1A. KLF, Krüppel-like factor; VSMC, vascular smooth muscle cell; HDAC, histone deacetylase; miR, microRNA; TNF-α, tumor necrosis factor alpha; IL-1β, interleukin-1 beta; RXR, retinoid X receptor; RAR, retinoid acid receptor; Cdkn1a, cyclin-dependent kinase inhibitor 1a.

Review

05 February 2018

Krüppel-Like Factors in Vascular Inflammation: Mechanistic Insights and Therapeutic Potential

David R. Sweet

, 2 more and

Mukesh K. Jain

12,597 views

86 citations

Vein graft remodeling. Damage caused by graft handling and distension during the high-pressure check for leakage as well as implantation in the high blood pressure surrounding of the arterial circulation results in distention of the venous graft. Depending on local and systemic influences like inflammatory factors, this can result in inward remodeling characterized by intimal hyperplasia and a reduced lumen or outward remodeling characterized by moderate intimal hyperplasia and an increased lumen.

Review

24 January 2018

Inflammation in Vein Graft Disease

Margreet R. de Vries

and

Paul H. A. Quax

9,814 views

87 citations

Inflammatory pathways that are currently used or may represent therapeutic targets to reduce vascular risk in diabetes. Current therapies and others in development focus on improving the endothelial cell function and reducing vascular inflammation. Established therapies to target endothelial dysfunction are angiotensin converting (ACE) inhibitors, angiotensin II-receptor blockers (ARBs), beta blockers, calcium channel blockers, and glitazones, whereas agents such as phosphodiesterase-5 inhibitors, endothelial nitric oxide synthase (eNOS) transcription enhancer, and microRNAs represent potential future therapies. Statins are widely used to reduce vascular risk and in addition to their cholesterol lowering effect they reduce vascular inflammation. Other potential targets to reduce vascular inflammation include of phospholipase A2 (PLA2) inhibitors as well as interleukin (IL)-1 antagonists and antioxidants.

Review

19 January 2018

Thrombosis and Vascular Inflammation in Diabetes: Mechanisms and Potential Therapeutic Targets

Nikoletta Pechlivani

and

Ramzi A. Ajjan

7,121 views

86 citations

Mechanisms of efferocytosis. (A) Macrophages interact with phosphatidylserine (PtdSer) externalized on apoptotic cells either directly or indirectly, through bridging molecules. Many PtdSer receptors stimulate ELMO–DOCK180 interactions to activate Rac1 and polymerize actin around the phagosome. Simultaneously, macrophages trigger Drp1-mediated mitochondrial fission to drive calcium-dependent vesicular trafficking. Once internalized, autophagic machinery is used to conjugate lipids to LC3 bound to phagosomes, which drives phagolysosomal fusion and subsequent apoptotic cell degradation. (B) In pathological settings such as advanced atherosclerosis, one or more of these processes can become defective, leading to inefficient clearance of apoptotic cells and subsequent necrosis and inflammation. For example, in advanced atherosclerosis, apoptotic cells can inappropriately express the “don’t eat-me” signal CD47, or cell-surface receptors can get proteolytically cleaved, such as with MerTK.

Review

08 January 2018

Mechanisms and Consequences of Defective Efferocytosis in Atherosclerosis

Arif Yurdagul

, 3 more and

Ira A. Tabas

Efficient clearance of apoptotic cells, termed efferocytosis, critically regulates normal homeostasis whereas defective uptake of apoptotic cells results in chronic and non-resolving inflammatory diseases, such as advanced atherosclerosis. Monocyte-derived macrophages recruited into developing atherosclerotic lesions initially display efficient efferocytosis and temper inflammatory responses, processes that restrict plaque progression. However, during the course of plaque development, macrophages undergo cellular reprogramming that reduces efferocytic capacity, which results in post-apoptotic necrosis of apoptotic cells and inflammation. Furthermore, defective efferocytosis in advanced atherosclerosis is a major driver of necrotic core formation, which can trigger plaque rupture and acute thrombotic cardiovascular events. In this review, we discuss the molecular and cellular mechanisms that regulate efferocytosis, how efferocytosis promotes the resolution of inflammation, and how defective efferocytosis leads to the formation of clinically dangerous atherosclerotic plaques.

21,322 views

236 citations