White and brown adipose tissues are hypervascularized and the adipose vasculature displays phenotypic and functional plasticity to coordinate with metabolic demands of adipocytes. Blood vessels not ...only supply nutrients and oxygen to nourish adipocytes, they also serve as a cellular reservoir to provide adipose precursor and stem cells that control adipose tissue mass and function. Multiple signaling molecules modulate the complex interplay between the vascular system and the adipocytes. Understanding fundamental mechanisms by which angiogenesis and vasculatures modulate adipocyte functions may provide new therapeutic options for treatment of obesity and metabolic disorders by targeting the adipose vasculature.
Effective treatment of patients with severe COVID‐19 to reduce mortality remains one of the most challenging medical issues in controlling unpredictable emergencies caused by the global pandemics. ...Unfortunately, such effective therapies are not available at this time of writing. In this article, I discuss the possibility of repurposing clinically available anti‐VEGF (vascular endothelial growth factor) drugs that are routinely used in oncology and ophthalmology areas for effective treatment of patients with severe and critical COVID‐19. Our preliminary findings from a clinical trial support the therapeutic concept of using anti‐VEGF for treating patients with severe COVID‐19 to reduce mortality. The aim of this article is to further provide mechanistic insights into the role of VEGF in causing pathological changes during COVID‐19 infection.
Leaking plasma from blood vessels triggered by COVID‐19 infection plays a crucial role in causing pulmonary atelectasis (lung collapse), which fills up the lung air sacs with liquid and the lung becomes deflated. If sufficiently large areas of the lung tissue become deflated by this problem, the lung tissue can no longer take enough air and oxygen for the entire body and patients suffer from life‐threatening shortness of breath. This article discusses the possibility of repurposing clinically available drugs designed for treating cancer and eye diseases for the benefit of treating patients with severe COVID‐19 by blocking vascular leakage.
Metastasis is the leading cause of cancer-associated mortality and the underlying mechanisms of cancer metastasis remain elusive. Both blood and lymphatic vasculatures are essential structures for ...mediating distal metastasis. The vasculature plays multiple functions, including accelerating tumor growth, sustaining the tumor microenvironment, supplying growth and invasive signals, promoting metastasis, and causing cancer-associated systemic disease. VEGF is one of the key angiogenic factors in tumors and participates in the initial stage of tumor development, progression and metastasis. Consequently, VEGF and its receptor-mediated signaling pathways have become one of the most important therapeutic targets for treating various cancers. Today, anti-VEGF-based antiangiogenic drugs (AADs) are widely used in the clinic for treating different types of cancer in human patients. Despite nearly 20-year clinical experience with AADs, the impact of these drugs on cancer metastasis and systemic disease remains largely unknown. In this review article, we focus our discussion on tumor VEGF in cancer metastasis and systemic disease and mechanisms underlying AADs in clinical benefits.
•VEGF-induced primitive vasculatures provide a structural basis for the dissemination of cancer cells into the circulation.•VEGF participates in metastatic niche formation and re-growth of metastatic tumors in distal organs.•VEGF and its related family members are involved in lymphatic metastasis.•Circulating VEGF targets non-tumor vasculatures in healthy tissues and organs to cause systemic disease.•Novel mechanistic insights into survival benefits of antiangiogenic drugs by blocking VEGF functions.
Nanotechnology could improve our understanding of the pathophysiology of atherosclerosis and contribute to the development of novel diagnostic and therapeutic strategies to further reduce the risk of ...cardiovascular disease. Macrophages have key roles in atherosclerosis progression and, therefore, macrophage-associated pathological processes are important targets for both diagnostic imaging and novel therapies for atherosclerosis. In this Review, we highlight efforts in the past two decades to develop imaging techniques and to therapeutically manipulate macrophages in atherosclerotic plaques with the use of rationally designed nanoparticles. We review the latest progress in nanoparticle-based imaging modalities that can specifically target macrophages. Using novel molecular imaging technology, these modalities enable the identification of advanced atherosclerotic plaques and the assessment of the therapeutic efficacy of medical interventions. Additionally, we provide novel perspectives on how macrophage-targeting nanoparticles can deliver a broad range of therapeutic payloads to atherosclerotic lesions. These nanoparticles can suppress pro-atherogenic macrophage processes, leading to improved resolution of inflammation and stabilization of plaques. Finally, we propose future opportunities for novel diagnostic and therapeutic strategies and provide solutions to challenges in this area for the purpose of accelerating the clinical translation of nanomedicine for the treatment of atherosclerotic vascular disease.
Current pharmacotherapeutic options for treating obesity and related metabolic disorders remain limited and ineffective. Emerging evidence shows that modulators of angiogenesis affect the expansion ...and metabolism of fat mass by regulating the growth and remodelling of the adipose tissue vasculature. Pharmacological manipulation of adipose tissue neovascularization by angiogenic stimulators and inhibitors might therefore offer a novel therapeutic option for the treatment of obesity and related metabolic disorders. This Perspective discusses recent progress in understanding the molecular mechanisms that control adipose tissue angiogenesis and in defining potential new vascular targets and approaches for the treatment of this group of diseases.
Highlights • Activaton of PDGF signaling often exists in the tumor microenvironment. • PDGFs promote tumor growth by targeting malignant and non-malignant cells. • PDGFs often interplay with other ...factors to promote tumor growth synergistically. • Targeting PDGFs and PDGFRs for cancer therapy remains a challenging issue.
Systemic administration of antiangiogenic drugs that target components of the vascular endothelial growth factor A (VEGF-A; VEGF) signal transduction pathway has become a viable therapeutic option ...for patients with various types of cancer. Nevertheless, these drugs can drive alterations in healthy vasculatures, which in turn are associated with adverse effects in healthy tissues. VEGF is crucial for vascular homeostasis and the maintenance of vascular integrity and architecture in endocrine organs. Given these critical physiological functions, systemic delivery of drugs that target VEGF signalling can block VEGF-mediated vascular functions in endocrine organs, such as the thyroid gland, and lead to endocrine dysfunction, including hypothyroidism, adrenal insufficiency and altered insulin sensitivity. This Review discusses emerging evidence from preclinical and clinical studies that contributes to understanding the mechanisms that underlie the vascular changes and subsequent modulations of endocrine function that are induced by targeted inhibition of VEGF signalling. Understanding these mechanisms is crucial for the design of antiangiogenic drugs with minimal associated adverse effects that will enable effective treatment of patients with cancer.
...antiangiogenic drugs are routinely used in the clinic for the treatment of various cancers and ocular diseases. Because the topic of angiogenesis in regulating lipid metabolism and metabolic ...diseases was recently discussed in another issue of the Chinese Medical Journal,4 we exclude this topic in this issue. ...preclinical and early clinical studies have already demonstrated benefits for treatment of cardiovascular disease, infectious disease, inflammatory disease, and metabolic disease. ...targeting angiogenesis in monotherapy and combination therapy settings provides immense opportunities for effective treatment of various diseases.
Vascular endothelial growth factor-A (VEGF-A) is a key target for new antiangiogenic drugs for the treatment of both malignant and nonmalignant human diseases. Vascular effects of VEGF family members ...are mainly mediated by VEGF receptor 2 (VEGFR2). Conversely, the function and signaling of VEGFR1, which is present on endothelial and nonendothelial cells, are poorly understood. Intriguingly, two of five members in the VEGF family--VEGF-B and placental growth factor (PlGF)--are exclusive ligands for VEGFR1 and do not interact with the other VEGFRs, VEGFR2 and VEGFR3. These VEGFR1-specific ligands may be important therapeutic targets for the treatment of cancer. This Review discusses the distinctive roles of VEGFR1 and its ligands PlGF and VEGF-B in the mediation of angiogenic signaling and considers the therapeutic potential of targeting these particular vascular factors.
Tumor metastasis is a hallmark of cancer. Metastatic cancer cells often reside in distal tissues and organs in their dormant state. Mechanisms underlying the pre-metastatic niche formation are poorly ...understood. Here we show that in a colorectal cancer (CRC) model, primary tumors release integrin beta-like 1 (ITGBL1)-rich extracellular vesicles (EVs) to the circulation to activate resident fibroblasts in remote organs. The activated fibroblasts induce the pre-metastatic niche formation and promote metastatic cancer growth by secreting pro-inflammatory cytokine, such as IL-6 and IL-8. Mechanistically, the primary CRC-derived ITGBL1-enriched EVs stimulate the TNFAIP3-mediated NF-κB signaling pathway to activate fibroblasts. Consequently, the activated fibroblasts produce high levels of pro-inflammatory cytokines to promote metastatic cancer growth. These findings uncover a tumor-stromal interaction in the metastatic tumor microenvironment and an intimate signaling communication between primary tumors and metastases through the ITGBL1-loaded EVs. Targeting the EVs-ITGBL1-CAFs-TNFAIP3-NF-κB signaling axis provides an attractive approach for treating metastatic diseases.
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