Angiopoietin-Like Proteins: Cardiovascular Biology and Therapeutic Targeting for the Prevention of Cardiovascular Diseases

Thorin, Éric; Labbé, Pauline; Lambert, M.; Mury, Pauline; Dagher, Olina; Miquel, Géraldine; Thorin‐Trescases, Nathalie

doi:10.1016/j.cjca.2023.06.002

Cited by 9 publications

(6 citation statements)

References 214 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, consistent with the lack of microvascular rarefaction in Igf1r KD brains, we did not observe changes in gene expression indicating an overall activation or inhibition of angiogenesis. We observed a few changes in genes that mapped to GO terms characteristic of a pro-angiogenic/anti-rarefaction phenotype [e.g., “sprouting angiogenesis” (GO:0002040), “positive regulation of angiogenesis” (GO:0045766, and “positive regulation of vasculature development” (GO:1904018)] in Igf1r KD brains such as upregulation of the VEGF receptor Flt4 and Mmp9 , and downregulation of the angiogenesis inhibitor Angptl1 ( Figures 7A, B ) in Igf1r KD vs. control ( Cao et al, 2006 ; Liu et al, 2018 ; Zhang et al, 2022 ; Thorin et al, 2023 ). However, we did not observe changes in other pro-angiogenic genes in the panel, including the growth factors Vegfa, Vegfb, Vegfc, Figf, Pdgf , or Ctgf .…”

Section: Resultsmentioning

confidence: 99%

IGF1R deficiency in vascular smooth muscle cells impairs myogenic autoregulation and cognition in mice

Miller,

Bickel,

Tarantini

et al. 2024

Front. Aging Neurosci.

View full text Add to dashboard Cite

IntroductionCerebrovascular pathologies contribute to cognitive decline during aging, leading to vascular cognitive impairment and dementia (VCID). Levels of circulating insulin-like growth factor 1 (IGF-1), a vasoprotective hormone, decrease during aging. Decreased circulating IGF-1 in animal models leads to the development of VCID-like symptoms, but the cellular mechanisms underlying IGF-1-deficiency associated pathologies in the aged cerebrovasculature remain poorly understood. Here, we test the hypothesis that vascular smooth muscle cells (VSMCs) play an integral part in mediating the vasoprotective effects of IGF-1.MethodsWe used a hypertension-based model of cerebrovascular dysfunction in mice with VSMC-specific IGF-1 receptor (Igf1r) deficiency and evaluated the development of cerebrovascular pathologies and cognitive dysfunction.ResultsVSMC-specific Igf1r deficiency led to impaired cerebral myogenic autoregulation, independent of blood pressure changes, which was also associated with impaired spatial learning and memory function as measured by radial arm water maze and impaired motor learning measured by rotarod. In contrast, VSMC-specific IGF-1 receptor knockdown did not lead to cerebral microvascular rarefaction.DiscussionThese studies suggest that VSMCs are key targets for IGF-1 in the context of cerebrovascular health, playing a role in vessel stability alongside other cells in the neurovascular unit, and that VSMC dysfunction in aging likely contributes to VCID.

show abstract

Section: Resultsmentioning

confidence: 99%

IGF1R deficiency in vascular smooth muscle cells impairs myogenic autoregulation and cognition in mice

Miller,

Bickel,

Tarantini

et al. 2024

Front. Aging Neurosci.

View full text Add to dashboard Cite

show abstract

“…Beyond their role as angiogenic factors, ANGPTLs also exhibit multifaceted functions, including involvement in chronic inflammation, redox regulation, glucose metabolism, and lipid metabolism. 32 Comprehensive understanding of ANGPTLs and their versatile functions offers valuable insights into potential therapeutic targets and diagnostic markers across a spectrum of health conditions. The stimulation of endothelial cells by ANGPTL7 has been observed to exert a multifaceted impact.…”

Section: ■ Discussionmentioning

confidence: 99%

Olink Profiling of Aqueous Humor Identifies Novel Biomarkers for Wet Age-Related Macular Degeneration

Liu,

Zhang,

Zhang

et al. 2024

J. Proteome Res.

View full text Add to dashboard Cite

“…In particular, PDGF and the angiopoietins exert their functions on the endothelium in a paracrine manner through their binding to, or their expression by, perivascular mural cells. In addition, angiopoietins regulate vascular homeostasis and promote vessel stability through the recruitment of mural cells and mediate their interactions with the endothelium ( 71 ). Among other potent angiogenic molecules are angiopoietin-like 4 ( 72 ), apelin ( 73 ), Frizzled A ( 74 , 75 ), thrombomodulin ( 76 ), AGGF1 ( 77 ), Slit3 ( 78 ), as well as a plethora of pro-angiogenic peptides, the therapeutic potential of which is reviewed elsewhere ( 79 ).…”

Section: Lrg1 and Angiogenesismentioning

confidence: 99%

The disruptive role of LRG1 on the vasculature and perivascular microenvironment

Dritsoula,

Camilli,

Moss

et al. 2024

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

The establishment of new blood vessels, and their subsequent stabilization, is a critical process that facilitates tissue growth and organ development. Once established, vessels need to diversify to meet the specific needs of the local tissue and to maintain homeostasis. These processes are tightly regulated and fundamental to normal vessel and tissue function. The mechanisms that orchestrate angiogenesis and vessel maturation have been widely studied, with signaling crosstalk between endothelium and perivascular cells being identified as an essential component. In disease, however, new vessels develop abnormally, and existing vessels lose their specialization and function, which invariably contributes to disease progression. Despite considerable research into the vasculopathic mechanisms in disease, our knowledge remains incomplete. Accordingly, the identification of angiocrine and angiopathic molecules secreted by cells within the vascular microenvironment, and their effect on vessel behaviour, remains a major research objective. Over the last decade the secreted glycoprotein leucine-rich α-2 glycoprotein 1 (LRG1), has emerged as a significant vasculopathic molecule, stimulating defective angiogenesis, and destabilizing the existing vasculature mainly, but not uniquely, by altering both canonical and non-canonical TGF-β signaling in a highly cell and context dependent manner. Whilst LRG1 does not possess any overt homeostatic role in vessel development and maintenance, growing evidence provides a compelling case for LRG1 playing a pleiotropic role in disrupting the vasculature in many disease settings. Thus, LRG1 has now been reported to damage vessels in various disorders including cancer, diabetes, chronic kidney disease, ocular disease, and lung disease and the signaling processes that drive this dysfunction are being defined. Moreover, therapeutic targeting of LRG1 has been widely proposed to re-establish a quiescent endothelium and normalized vasculature. In this review, we consider the current status of our understanding of the role of LRG1 in vascular pathology, and its potential as a therapeutic target.

show abstract

Angiopoietin-Like Proteins: Cardiovascular Biology and Therapeutic Targeting for the Prevention of Cardiovascular Diseases

Cited by 9 publications

References 214 publications

IGF1R deficiency in vascular smooth muscle cells impairs myogenic autoregulation and cognition in mice

IGF1R deficiency in vascular smooth muscle cells impairs myogenic autoregulation and cognition in mice

Olink Profiling of Aqueous Humor Identifies Novel Biomarkers for Wet Age-Related Macular Degeneration

The disruptive role of LRG1 on the vasculature and perivascular microenvironment

Contact Info

Product

Resources

About