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      Systems biology of angiogenesis signaling: Computational models and omics

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          Abstract

          Angiogenesis is a highly regulated multiscale process that involves a plethora of cells, their cellular signal transduction, activation, proliferation, differentiation, as well as their intercellular communication. The coordinated execution and integration of such complex signaling programs is critical for physiological angiogenesis to take place in normal growth, development, exercise, and wound healing, while its dysregulation is critically linked to many major human diseases such as cancer, cardiovascular diseases, and ocular disorders; it is also crucial in regenerative medicine. Although huge efforts have been devoted to drug development for these diseases by investigation of angiogenesis-targeted therapies, only a few therapeutics and targets have proved effective in humans due to the innate multiscale complexity and nonlinearity in the process of angiogenic signaling. As a promising approach that can help better address this challenge, systems biology modeling allows the integration of knowledge across studies and scales and provides a powerful means to mechanistically elucidate and connect the individual molecular and cellular signaling components that function in concert to regulate angiogenesis. In this review, we summarize and discuss how systems biology modeling studies, at the pathway-, cell-, tissue-, and whole body-levels, have advanced our understanding of signaling in angiogenesis and thereby delivered new translational insights for human diseases.

          This article is categorized under:

          Cardiovascular Diseases > Computational Models Cancer > Computational Models

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          Most cited references249

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          Heart Disease and Stroke Statistics—2021 Update: A Report From the American Heart Association

          The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2021 Statistical Update is the product of a full year’s worth of effort by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year’s edition includes data on the monitoring and benefits of cardiovascular health in the population, an enhanced focus on social determinants of health, adverse pregnancy outcomes, vascular contributions to brain health, the global burden of cardiovascular disease, and further evidence-based approaches to changing behaviors related to cardiovascular disease. Each of the 27 chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. The Statistical Update represents a critical resource for the lay public, policy makers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.
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            Macrophage plasticity and polarization: in vivo veritas.

            Diversity and plasticity are hallmarks of cells of the monocyte-macrophage lineage. In response to IFNs, Toll-like receptor engagement, or IL-4/IL-13 signaling, macrophages undergo M1 (classical) or M2 (alternative) activation, which represent extremes of a continuum in a universe of activation states. Progress has now been made in defining the signaling pathways, transcriptional networks, and epigenetic mechanisms underlying M1-M2 or M2-like polarized activation. Functional skewing of mononuclear phagocytes occurs in vivo under physiological conditions (e.g., ontogenesis and pregnancy) and in pathology (allergic and chronic inflammation, tissue repair, infection, and cancer). However, in selected preclinical and clinical conditions, coexistence of cells in different activation states and unique or mixed phenotypes have been observed, a reflection of dynamic changes and complex tissue-derived signals. The identification of mechanisms and molecules associated with macrophage plasticity and polarized activation provides a basis for macrophage-centered diagnostic and therapeutic strategies.
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              Angiogenesis in life, disease and medicine.

              The growth of blood vessels (a process known as angiogenesis) is essential for organ growth and repair. An imbalance in this process contributes to numerous malignant, inflammatory, ischaemic, infectious and immune disorders. Recently, the first anti-angiogenic agents have been approved for the treatment of cancer and blindness. Angiogenesis research will probably change the face of medicine in the next decades, with more than 500 million people worldwide predicted to benefit from pro- or anti-angiogenesis treatments.
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                Author and article information

                Journal
                9918227353306676
                50765
                WIREs Mech Dis
                WIREs Mech Dis
                WIREs mechanisms of disease
                2692-9368
                20 June 2022
                July 2022
                30 December 2021
                15 July 2022
                : 14
                : 4
                : e1550
                Affiliations
                [1 ]Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
                [2 ]School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu, China
                Author notes

                AUTHOR CONTRIBUTIONS

                Yu Zhang: Conceptualization (equal); investigation (equal); writing – original draft (equal); writing – review and editing (equal). Hanwen Wang: Investigation (equal); writing – original draft (equal). Rebeca Hannah M Oliveira: Investigation (equal); writing – original draft (equal). Chen Zhao: Conceptualization (lead); investigation (equal); supervision (lead); writing – original draft (equal); writing – review and editing (equal). Aleksander S Popel: Conceptualization (equal); funding acquisition (lead); supervision (lead); writing – review and editing (equal).

                Correspondence: Chen Zhao, School of Pharmacy, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu, 211166, China. zcshinchon4677@ 123456outlook.com
                Author information
                http://orcid.org/0000-0003-3643-6589
                http://orcid.org/0000-0003-1361-8419
                Article
                NIHMS1817547
                10.1002/wsbm.1550
                9243197
                34970866
                40cad065-f5f5-4f77-8296-1e3da3d9d42e

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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                Categories
                Article

                angiogenesis,endothelial cell,mathematical model,multiscale systems biology,omics,signal transduction

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