PDGFD switches on stem cell endothelial commitment
AbstractThe critical factors regulating stem cell endothelial commitment and renewal remain not well understood. Here, using loss- and gain-of-function assays together with bioinformatic analysis and multiple model systems, we show that PDGFD is an essential factor that switches on endothelial commitment of embryonic stem cells (ESCs). PDGFD genetic deletion or knockdown inhibits ESC differentiation into EC lineage and increases ESC self-renewal, and PDGFD overexpression activates ESC differentiation towards ECs. RNA sequencing reveals a critical requirement of PDGFD for the expression of vascular-differentiation related g...
Source: Angiogenesis - July 20, 2022 Category: Molecular Biology Source Type: research

Angiogenesis in adipose tissue and obesity
AbstractWhile most tissues exhibit their greatest growth during development, adipose tissue is capable of additional massive expansion in adults. Adipose tissue expandability is advantageous when temporarily storing fuel for use during fasting, but becomes pathological upon continuous food intake, leading to obesity and its many comorbidities. The dense vasculature of adipose tissue provides necessary oxygen and nutrients, and supports delivery of fuel to and from adipocytes under fed or fasting conditions. Moreover, the vasculature of adipose tissue comprises a major niche for multipotent progenitor cells, which give rise...
Source: Angiogenesis - July 20, 2022 Category: Molecular Biology Source Type: research

PDGFD switches on stem cell endothelial commitment
AbstractThe critical factors regulating stem cell endothelial commitment and renewal remain not well understood. Here, using loss- and gain-of-function assays together with bioinformatic analysis and multiple model systems, we show that PDGFD is an essential factor that switches on endothelial commitment of embryonic stem cells (ESCs). PDGFD genetic deletion or knockdown inhibits ESC differentiation into EC lineage and increases ESC self-renewal, and PDGFD overexpression activates ESC differentiation towards ECs. RNA sequencing reveals a critical requirement of PDGFD for the expression of vascular-differentiation related g...
Source: Angiogenesis - July 20, 2022 Category: Molecular Biology Source Type: research

Angiogenesis in adipose tissue and obesity
AbstractWhile most tissues exhibit their greatest growth during development, adipose tissue is capable of additional massive expansion in adults. Adipose tissue expandability is advantageous when temporarily storing fuel for use during fasting, but becomes pathological upon continuous food intake, leading to obesity and its many comorbidities. The dense vasculature of adipose tissue provides necessary oxygen and nutrients, and supports delivery of fuel to and from adipocytes under fed or fasting conditions. Moreover, the vasculature of adipose tissue comprises a major niche for multipotent progenitor cells, which give rise...
Source: Angiogenesis - July 20, 2022 Category: Molecular Biology Source Type: research

S100A4-dependent glycolysis promotes lymphatic vessel sprouting in tumor
AbstractTumor-induced lymphangiogenesis promotes the formation of new lymphatic vessels, contributing to lymph nodes (LNs) metastasis of tumor cells in both mice and humans. Vessel sprouting appears to be a critical step in this process. However, how lymphatic vessels sprout during tumor lymphangiogenesis is not well-established. Here, we report that S100A4 expressed in lymphatic endothelial cells (LECs) promotes lymphatic vessel sprouting in a growing tumor by regulating glycolysis. In mice, the loss of S100A4 in a whole body (S100A4−/−), or specifically in LECs (S100A4ΔLYVE1) leads to impaired tumor lymphangiogenesi...
Source: Angiogenesis - July 12, 2022 Category: Molecular Biology Source Type: research

Therapeutic angiogenesis for patients with no-option critical limb ischemia by adipose-derived regenerative cells: TACT-ADRC multicenter trial
ConclusionsImplantation of autologous ADRCs could be safe and effective for the achievement of therapeutic angiogenesis in the multicenter settings, as a result in no major adverse event, optimal survival rate, and limb salvage for patients with no-conventional option against critical limb ischemia.TRN: jRCTb040190118; Date: Nov. 24th, 2015. (Source: Angiogenesis)
Source: Angiogenesis - July 8, 2022 Category: Molecular Biology Source Type: research

Microvascular and proteomic signatures overlap in COVID-19 and bacterial sepsis: the MICROCODE study
ConclusionOur data imply a common biological host response of microvascular injury in both bacterial  sepsis and COVID-19. A distinct plasma signature correlates with endothelial health and improved outcomes, while a counteracting response is associated with glycocalyx breakdown and high mortality. Microvascular health biomarkers are powerful predictors of clinical outcomes.Graphical abstract (Source: Angiogenesis)
Source: Angiogenesis - June 20, 2022 Category: Molecular Biology Source Type: research

In vitro grafting of hepatic spheroids and organoids on a microfluidic vascular bed
AbstractWith recent progress in modeling liver organogenesis and regeneration, the lack of vasculature is becoming the bottleneck in progressing our ability to model human hepatic tissues in vitro. Here, we introduce a platform for routine grafting of liver and other tissues on an in vitro grown microvascular bed. The platform consists of 64 microfluidic chips patterned underneath a 384-well microtiter plate. Each chip allows the formation of a microvascular bed between two main lateral vessels by inducing angiogenesis. Chips consist of an open-top microfluidic chamber, which enables addition of a target tissue by manual o...
Source: Angiogenesis - June 15, 2022 Category: Molecular Biology Source Type: research

A novel somatic mutation in GNAQ in a capillary malformation provides insight into molecular pathogenesis
In this study, we sequenced skin biopsies of capillary malformations from 9 patients. We identified the R183Q mutation in nearly all samples, but one sample exhibited a Q209R mutation. This new mutation occurs at the same residue as the constitutively-activating Q209L mutation, commonly seen in tumors. However, Q209R is a rare variant in this gene. To compare the effect of the Q209R mutation on downstream signaling, we performed reporter assays with a GNAQ-responsive reporter co-transfected with either GNAQ WT, R183Q, Q209L, Q209R, or C9X (representing a null allele). Q209L showed the highest reporter activation, with R183...
Source: Angiogenesis - May 30, 2022 Category: Molecular Biology Source Type: research