Interdependence of Angiogenesis and Arteriogenesis in Development and Disease

Noble, Ferdinand le; Kupatt, Christian

doi:10.3390/ijms23073879

Cited by 9 publications

(6 citation statements)

References 63 publications

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“…Angiogenesis is the process of growing new blood vessels and is initiated by sprouting capillaries from the existing vasculature. It consists of several steps: the separation of pericyte, the migration and proliferation of endothelial cells, remodeling into capillary tubes, and the recruitment of pericytes/smooth muscle cells [ 36 , 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

Tenascin-C in Tissue Repair after Myocardial Infarction in Humans

Matsui

Torii

Hara

et al. 2023

IJMS

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Adverse ventricular remodeling after myocardial infarction (MI) is progressive ventricular dilatation associated with heart failure for weeks or months and is currently regarded as the most critical sequela of MI. It is explained by inadequate tissue repair due to dysregulated inflammation during the acute stage; however, its pathophysiology remains unclear. Tenascin-C (TNC), an original member of the matricellular protein family, is highly up-regulated in the acute stage after MI, and a high peak in its serum level predicts an increased risk of adverse ventricular remodeling in the chronic stage. Experimental TNC-deficient or -overexpressing mouse models have suggested the diverse functions of TNC, particularly its pro-inflammatory effects on macrophages. The present study investigated the roles of TNC during human myocardial repair. We initially categorized the healing process into four phases: inflammatory, granulation, fibrogenic, and scar phases. We then immunohistochemically examined human autopsy samples at the different stages after MI and performed detailed mapping of TNC in human myocardial repair with a focus on lymphangiogenesis, the role of which has recently been attracting increasing attention as a mechanism to resolve inflammation. The direct effects of TNC on human lymphatic endothelial cells were also assessed by RNA sequencing. The results obtained support the potential roles of TNC in the regulation of macrophages, sprouting angiogenesis, the recruitment of myofibroblasts, and the early formation of collagen fibrils during the inflammatory phase to the early granulation phase of human MI. Lymphangiogenesis was observed after the expression of TNC was down-regulated. In vitro results revealed that TNC modestly down-regulated genes related to nuclear division, cell division, and cell migration in lymphatic endothelial cells, suggesting its inhibitory effects on lymphatic endothelial cells. The present results indicate that TNC induces prolonged over-inflammation by suppressing lymphangiogenesis, which may be one of the mechanisms underlying adverse post-infarct remodeling.

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Section: Discussionmentioning

confidence: 99%

Tenascin-C in Tissue Repair after Myocardial Infarction in Humans

Matsui

Torii

Hara

et al. 2023

IJMS

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“…However, in retrospect this is not altogether unexpected: Primary angiogenic proteins, including VEGF-A, Flk1, Notch, DLL4, EphrinB2, and EphB4 that direct formation of the capillary plexus and arterial-venous trees during development, are required to be fully functional and expressed at precise times and concentrations for normal fetal and postnatal growth. 53 Accordingly, their genes are presumably under strong selective pressure against damaging alleles that would reduce protein activity or expression enough to impair formation of the correct vessel densities, diameters and branch-patterning that are required to optimize hydraulic conductance within tissue vasculatures. In contrast, deleterious polymorphisms within the primary genes and regulatory elements within the collaterogenesis pathway are less likely to be under such negative selection pressure.…”

Section: Discussionmentioning

confidence: 99%

Large differences in collateral blood vessel abundance among individuals arise from multiple genetic variants

Faber

Zhang

Xenakis

et al. 2023

J Cereb Blood Flow Metab

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Collateral blood flow varies greatly among humans for reasons that remain unclear, resulting in significant differences in ischemic tissue damage. A similarly large variation has also been found in mice that is caused by genetic background-dependent differences in the extent of collateral formation, termed collaterogenesis—a unique angiogenic process that occurs during development and determines collateral number and diameter in the adult. Previous studies have identified several quantitative trait loci (QTL) linked to this variation. However, understanding has been hampered by the use of closely related inbred strains that do not model the wide genetic variation present in the “outbred” human population. The Collaborative Cross (CC) multiparent mouse genetic reference panel was developed to address this limitation. Herein we measured the number and average diameter of cerebral collaterals in 60 CC strains, their 8 founder strains, 8 F1 crosses of CC strains selected for abundant versus sparse collaterals, and 2 intercross populations created from the latter. Collateral number evidenced 47-fold variation among the 60 CC strains, with 14% having poor, 25% poor-to-intermediate, 47% intermediate-to-good, and 13% good collateral abundance, that was associated with large differences in post-stroke infarct volume. Collateral number in skeletal muscle and intestine of selected high- and low-collateral strains evidenced the same relative abundance as in brain. Genome-wide mapping demonstrated that collateral abundance is a highly polymorphic trait. Subsequent analysis identified: 6 novel QTL circumscribing 28 high-priority candidate genes harboring putative loss-of-function polymorphisms (SNPs) associated with low collateral number; 335 predicted-deleterious SNPs present in their human orthologs; and 32 genes associated with vascular development but lacking protein coding variants. Six additional suggestive QTL (LOD > 4.5) were also identified in CC-wide QTL mapping. This study provides a comprehensive set of candidate genes for future investigations aimed at identifying signaling proteins within the collaterogenesis pathway whose variants potentially underlie genetic-dependent collateral insufficiency in brain and other tissues.

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“…The simultaneous activation of dual alpha and gamma PPARs agonists may provide superior glucose and lipid regulation compared to single subtype-selective drugs [ 59 , 60 ]. In addition, growth factors and cytokines that promote endothelial cell migration also regulate angiogenesis [ 61 , 62 ], proliferation [ 63 ], and survival to promote revascularization and tissue ischemia affected by T2D [ 64 , 65 ].…”

Section: Introductionmentioning

confidence: 99%

Partial Synthetic PPARƳ Derivative Ameliorates Aorta Injury in Experimental Diabetic Rats Mediated by Activation of miR-126-5p Pi3k/AKT/PDK 1/mTOR Expression

et al. 2022

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Type 2 diabetes mellitus (T2D) is a world wild health care issue marked by insulin resistance, a risk factor for the metabolic disorder that exaggerates endothelial dysfunction, increasing the risk of cardiovascular complications. Peroxisome proliferator-activated receptor PPAR) agonists have therapeutically mitigated hyperlipidemia and hyperglycemia in T2D patients. Therefore, we aimed to experimentally investigate the efficacy of newly designed synthetic PPARα/Ƴ partial agonists on a High-Fat Diet (HFD)/streptozotocin (STZ)-induced T2D. Female Wistar rats (200 ± 25 g body weight) were divided into four groups. The experimental groups were fed the HFD for three consecutive weeks before STZ injection (45 mg/kg/i.p) to induce T2D. Standard reference PPARƳ agonist pioglitazone and the partial synthetic PPARƳ (PIO; 20 mg/kg/BW, orally) were administered orally for 2 weeks after 72 h of STZ injection. The aorta tissue was isolated for biological ELISA, qRT-PCR, and Western blotting investigations for vascular inflammatory endothelial mediators endothelin-1 (ET-1), intracellular adhesion molecule 1 (ICAM-1), E-selectin, and anti-inflammatory vasoactive intestinal polypeptide (VIP), as well as microRNA126-5p and p-AKT/p-Pi3k/p-PDK-1/p-mTOR, endothelial Nitric Oxide Synthase (eNOS) immunohistochemical staining all are coupled with and histopathological examination. Our results revealed that HFD/STZ-induced T2D increased fasting blood glucose, ET-1, ICAM-1, E-selectin, and VIP levels, while decreasing the expression of both microRNA126-5p and p-AKT/p-Pi3k/p-PDK-1/p-mTOR phosphorylation. In contrast, the partial synthetic PPARƳ derivative evidenced a vascular alteration significantly more than reference PIO via decreasing (ET-1), ICAM-1, E-selectin, and VIP, along with increased expression of microRNA126-5p and p-AKT/p-Pi3k/p-PDK-1/p-mTOR. In conclusion, the partial synthetic PPARƳ derivative significantly affected HFD/STZ-induced T2D with vascular complications in the rat aorta.

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Interdependence of Angiogenesis and Arteriogenesis in Development and Disease

Cited by 9 publications

References 63 publications

Tenascin-C in Tissue Repair after Myocardial Infarction in Humans

Tenascin-C in Tissue Repair after Myocardial Infarction in Humans

Large differences in collateral blood vessel abundance among individuals arise from multiple genetic variants

Partial Synthetic PPARƳ Derivative Ameliorates Aorta Injury in Experimental Diabetic Rats Mediated by Activation of miR-126-5p Pi3k/AKT/PDK 1/mTOR Expression

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