Pathological angiogenesis: mechanisms and therapeutic strategies

Angiogenesis, Год журнала: 2023, Номер 26(3), С. 313 - 347

Опубликована: Апрель 15, 2023

In multicellular organisms, angiogenesis, the formation of new blood vessels from pre-existing ones, is an essential process for growth and development. Different mechanisms such as vasculogenesis, sprouting, intussusceptive, coalescent well vessel co-option, vasculogenic mimicry lymphangiogenesis, underlie vasculature. many pathological conditions, cancer, atherosclerosis, arthritis, psoriasis, endometriosis, obesity SARS-CoV-2(COVID-19), developmental angiogenic processes are recapitulated, but often done so without normal feedback that regulate ordinary spatial temporal patterns formation. Thus, angiogenesis presents challenges yet opportunities design vascular-directed therapies. Here, we provide overview recent insights into development highlight novel therapeutic strategies promote or inhibit to stabilize, reverse, even halt disease progression. our review, will also explore several additional aspects (the switch, hypoxia, angiocrine signals, endothelial plasticity, normalization, cell anergy) operate in parallel canonical speculate how these may be targeted with anti-angiogenic

Язык: Английский

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Hypoxia-induced signaling in the cardiovascular system: pathogenesis and therapeutic targets

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Ноя. 20, 2023

Hypoxia, characterized by reduced oxygen concentration, is a significant stressor that affects the survival of aerobic species and plays prominent role in cardiovascular diseases. From research history milestone events related to hypoxia development diseases, The "hypoxia-inducible factors (HIFs) switch" can be observed from both temporal spatial perspectives, encompassing occurrence progression (gradual decline concentration), acute chronic manifestations hypoxia, geographical characteristics (natural selection at high altitudes). Furthermore, signaling pathways are associated with natural rhythms, such as diurnal hibernation processes. In addition innate selection, it has been found epigenetics, postnatal factor, profoundly influences hypoxic response within system. Within this intricate process, interactions between different tissues organs system other systems context have established. Thus, time summarize construct multi-level regulatory framework mechanisms diseases for developing more therapeutic targets make reasonable advancements clinical research, including FDA-approved drugs ongoing trials, guide future practice field

Язык: Английский

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Targeted Therapy and Mechanisms of Drug Resistance in Breast Cancer

Cancers, Год журнала: 2023, Номер 15(4), С. 1320 - 1320

Опубликована: Фев. 19, 2023

Breast cancer is the most common cause of cancer-related death in women worldwide. Multidrug resistance (MDR) has been a large hurdle reducing BC rates. The drug mechanisms include increased efflux, enhanced DNA repair, senescence escape, epigenetic alterations, tumor heterogeneity, microenvironment (TME), and epithelial-to-mesenchymal transition (EMT), which make it challenging to overcome. This review aims explain further, identify viable targets, elucidate how those targets relate progression resistance.

Язык: Английский

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An insight into brown/beige adipose tissue whitening, a metabolic complication of obesity with the multifactorial origin

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Фев. 16, 2023

Brown adipose tissue (BAT), a thermoregulatory organ known to promote energy expenditure, has been extensively studied as potential avenue combat obesity. Although BAT is the opposite of white (WAT) which responsible for storage, shares thermogenic capacity with beige that emerges from WAT depots. This unsurprising both and display huge difference in terms their secretory profile physiological role. In obesity, content declines these tissues acquire characteristics via process called “whitening”. rarely explored its implication whether it contributes or exacerbates Emerging research demonstrated BAT/beige whitening sophisticated metabolic complication obesity linked multiple factors. The current review provides clarification on influence various factors such diet, age, genetics, thermoneutrality, chemical exposure whitening. Moreover, defects mechanisms underpin are described. Notably, can be marked by accumulation large unilocular lipid droplets, mitochondrial degeneration, collapsed capacity, virtue dysfunction, devascularization, autophagy, inflammation.

Язык: Английский

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The evolving functions of the vasculature in regulating adipose tissue biology in health and obesity

Nature Reviews Endocrinology, Год журнала: 2023, Номер 19(12), С. 691 - 707

Опубликована: Сен. 25, 2023

Язык: Английский

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Adipose Tissue Remodeling in Pathophysiology

Annual Review of Pathology Mechanisms of Disease, Год журнала: 2022, Номер 18(1), С. 71 - 93

Опубликована: Сен. 7, 2022

Rather than serving as a mere onlooker, adipose tissue is complex endocrine organ and active participant in disease initiation progression. Disruptions of biological processes operating within can disturb healthy systemic physiology, the sequelae which include metabolic disorders such obesity type 2 diabetes. A burgeoning interest field research has allowed for elucidation regulatory networks underlying both function dysfunction. Despite this progress, few diseases are treated by targeting maladaptation adipose, an oft-overlooked organ. In review, we elaborate on distinct subtypes adipocytes, their developmental origins secretory roles, dynamic interplay at work itself. Central to discussion relationship between states, including obesity, cachexia, infectious diseases, aim leverage our wealth knowledge development novel targeted therapeutics.

Язык: Английский

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Single-cell profiling of vascular endothelial cells reveals progressive organ-specific vulnerabilities during obesity

Nature Metabolism, Год журнала: 2022, Номер 4(11), С. 1591 - 1610

Опубликована: Ноя. 18, 2022

Obesity promotes diverse pathologies, including atherosclerosis and dementia, which frequently involve vascular defects endothelial cell (EC) dysfunction. Each organ has distinct EC subtypes, but whether ECs are differentially affected by obesity is unknown. Here we use single-cell RNA sequencing to analyze transcriptomes of ~375,000 from seven organs in male mice at progressive stages identify organ-specific vulnerabilities. We find that deregulates gene expression networks, lipid handling, metabolic pathways AP1 transcription factor inflammatory signaling, an organ- EC-subtype-specific manner. The transcriptomic aberrations worsen with sustained only partially mitigated dietary intervention weight loss. For example, substantially attenuates dysregulation liver, not kidney, transcriptomes. Through integration human genome-wide association study data, further a subset disease risk genes induced obesity. Our work catalogs the impact on endothelium, constitutes useful resource reveals leads for investigation as potential therapeutic targets.

Язык: Английский

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Angiocrine polyamine production regulates adiposity

Nature Metabolism, Год журнала: 2022, Номер 4(3), С. 327 - 343

Опубликована: Март 14, 2022

Язык: Английский

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Environmental microplastics (EMPs) exposure alter the differentiation potential of mesenchymal stromal cells

Environmental Research, Год журнала: 2022, Номер 214, С. 114088 - 114088

Опубликована: Авг. 13, 2022

Язык: Английский

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The impact of cellular senescence in human adipose tissue

Journal of Cell Communication and Signaling, Год журнала: 2023, Номер 17(3), С. 563 - 573

Опубликована: Май 17, 2023

Abstract In the last decades prevalence of obesity has increased dramatically, and worldwide epidemic related metabolic diseases contributed to an interest for adipose tissue (AT), primary site storage lipids, as a metabolically dynamic endocrine organ. Subcutaneous AT is depot with largest capacity store excess energy when its limit reached hypertrophic obesity, local inflammation, insulin resistance ultimately type 2 diabetes (T2D) will develop. Hypertrophic also associated dysfunctional adipogenesis, depending on inability recruit differentiate new mature cells. Lately, cellular senescence (CS), aging mechanism defined irreversible growth arrest that occurs in response various stressors, such telomere shortening, DNA damage oxidative stress, gained lot attention regulator tissues aging-associated conditions. The abundance senescent cells increases not only but independent age. Senescent characterized by cells, decreased sensitivity lipid storage. resident progenitor (APC), non-proliferating microvascular endothelial are affected burden. Dysfunctional APC have both impaired adipogenic proliferative capacity. Interestingly, human from obese hyperinsulinemic individuals been shown re-enter cell cycle senesce, which indicates endoreplication. CS was found be more pronounced T2D individuals, compared matched non-diabetic Graphical abstract Factors

Язык: Английский

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