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Biomedicine & Pharmacotherapy =... Jul 2024Intracranial atherosclerotic stenosis (ICAS) is a pathological condition characterized by progressive narrowing or complete blockage of intracranial blood vessels caused... (Review)
Review
Intracranial atherosclerotic stenosis (ICAS) is a pathological condition characterized by progressive narrowing or complete blockage of intracranial blood vessels caused by plaque formation. This condition leads to reduced blood flow to the brain, resulting in cerebral ischemia and hypoxia. Ischemic stroke (IS) resulting from ICAS poses a significant global public health challenge, especially among East Asian populations. However, the underlying causes of the notable variations in prevalence among diverse populations, as well as the most effective strategies for preventing and treating the rupture and blockage of intracranial plaques, remain incompletely comprehended. Rupture of plaques, bleeding, and thrombosis serve as precipitating factors in the pathogenesis of luminal obstruction in intracranial arteries. Pericytes play a crucial role in the structure and function of blood vessels and face significant challenges in regulating the Vasa Vasorum (VV)and preventing intraplaque hemorrhage (IPH). This review aims to explore innovative therapeutic strategies that target the pathophysiological mechanisms of vulnerable plaques by modulating pericyte biological function. It also discusses the potential applications of pericytes in central nervous system (CNS) diseases and their prospects as a therapeutic intervention in the field of biological tissue engineering regeneration.
Topics: Pericytes; Humans; Animals; Intracranial Arteriosclerosis; Vasa Vasorum; Cerebral Arteries
PubMed: 38850658
DOI: 10.1016/j.biopha.2024.116870 -
Nature Neuroscience Jun 2024Fibrotic scar tissue formation occurs in humans and mice. The fibrotic scar impairs tissue regeneration and functional recovery. However, the origin of scar-forming...
Fibrotic scar tissue formation occurs in humans and mice. The fibrotic scar impairs tissue regeneration and functional recovery. However, the origin of scar-forming fibroblasts is unclear. Here, we show that stromal fibroblasts forming the fibrotic scar derive from two populations of perivascular cells after spinal cord injury (SCI) in adult mice of both sexes. We anatomically and transcriptionally identify the two cell populations as pericytes and perivascular fibroblasts. Fibroblasts and pericytes are enriched in the white and gray matter regions of the spinal cord, respectively. Both cell populations are recruited in response to SCI and inflammation. However, their contribution to fibrotic scar tissue depends on the location of the lesion. Upon injury, pericytes and perivascular fibroblasts become activated and transcriptionally converge on the generation of stromal myofibroblasts. Our results show that pericytes and perivascular fibroblasts contribute to the fibrotic scar in a region-dependent manner.
PubMed: 38849523
DOI: 10.1038/s41593-024-01678-4 -
The British Journal of Dermatology Jun 2024Infantile haemangioma (IH), the most common vascular tumour of infancy, is comprised of diverse cell types including endothelial cells, pericytes, fibroblasts and immune...
Infantile haemangioma (IH), the most common vascular tumour of infancy, is comprised of diverse cell types including endothelial cells, pericytes, fibroblasts and immune cells. IH is characterized by rapid proliferation followed by slow involution over 1 - 10 years. Most lesions regress spontaneously, but up to 10% can be disfiguring with complications that require further medical treatment. Recent research has revealed the biological characteristics of IH, highlighting the involvement of angiogenesis and vasculogenesis during tumour formation. Gene expression profiling has provided vital insights into these underlying biological processes, with some of the key IH-related pathways identified, including VEGF, RAAS, HIF-1α, Notch, PDGF, PI3K/Akt/mTOR, JAK/STAT, FGF, PPARγ, IGF. Further evidence suggests extracellular matrix factors and hormone receptors regulate IH progression. In this review, we explore the molecular mechanisms involved in the proliferating, plateau and involuting phases of IH. This involves identifying differentially expressed genes, targeted proteins, and key signalling pathways. This knowledge will increase the broader understanding of vascular development, tissue remodelling and angiogenesis.
PubMed: 38845569
DOI: 10.1093/bjd/ljae241 -
Communications Biology Jun 2024Pericyte dysfunction, with excessive migration, hyperproliferation, and differentiation into smooth muscle-like cells contributes to vascular remodeling in Pulmonary...
Pericyte dysfunction, with excessive migration, hyperproliferation, and differentiation into smooth muscle-like cells contributes to vascular remodeling in Pulmonary Arterial Hypertension (PAH). Augmented expression and action of growth factors trigger these pathological changes. Endogenous factors opposing such alterations are barely known. Here, we examine whether and how the endothelial hormone C-type natriuretic peptide (CNP), signaling through the cyclic guanosine monophosphate (cGMP) -producing guanylyl cyclase B (GC-B) receptor, attenuates the pericyte dysfunction observed in PAH. The results demonstrate that CNP/GC-B/cGMP signaling is preserved in lung pericytes from patients with PAH and prevents their growth factor-induced proliferation, migration, and transdifferentiation. The anti-proliferative effect of CNP is mediated by cGMP-dependent protein kinase I and inhibition of the Phosphoinositide 3-kinase (PI3K)/AKT pathway, ultimately leading to the nuclear stabilization and activation of the Forkhead Box O 3 (FoxO3) transcription factor. Augmentation of the CNP/GC-B/cGMP/FoxO3 signaling pathway might be a target for novel therapeutics in the field of PAH.
Topics: Humans; Pericytes; Natriuretic Peptide, C-Type; Cyclic GMP; Signal Transduction; Forkhead Box Protein O3; Cell Proliferation; Male; Female; Pulmonary Arterial Hypertension; Middle Aged; Hypertension, Pulmonary; Adult; Receptors, Atrial Natriuretic Factor; Cells, Cultured
PubMed: 38844781
DOI: 10.1038/s42003-024-06375-3 -
Arteriosclerosis, Thrombosis, and... Jun 2024Pulmonary hypertension (PH) is a common complication of systemic sclerosis (SSc) and a leading cause of mortality among patients with this disease. PH can also occur as...
BACKGROUND
Pulmonary hypertension (PH) is a common complication of systemic sclerosis (SSc) and a leading cause of mortality among patients with this disease. PH can also occur as an idiopathic condition (idiopathic pulmonary arterial hypertension). Investigation of transcriptomic alterations in vascular populations is critical to elucidating cellular mechanisms underlying pathobiology of SSc-associated and idiopathic PH.
METHODS
We analyzed single-cell RNA sequencing profiles of endothelial and perivascular mesenchymal populations from explanted lung tissue of patients with SSc-associated PH (n=16), idiopathic pulmonary arterial hypertension (n=3), and healthy controls (n=15). Findings were validated by immunofluorescence staining of explanted human lung tissue.
RESULTS
Three disease-associated endothelial populations emerged. Two angiogenic endothelial cell (EC) subtypes markedly expanded in SSc-associated PH lungs: tip ECs expressing canonical tip markers and and phalanx ECs expressing genes associated with vascular development, endothelial barrier integrity, and Notch signaling. Gene regulatory network analysis suggested enrichment of Smad1 and PPAR-γ (peroxisome proliferator-activated receptor-γ) regulon activities in these 2 populations, respectively. Mapping of potential ligand-receptor interactions highlighted Notch, apelin-APJ, and angiopoietin-Tie signaling pathways between angiogenic ECs and perivascular cells. Transitional cells, expressing both endothelial and pericyte/smooth muscle cell markers, provided evidence for the presence of endothelial-to-mesenchymal transition. Transcriptional programs associated with arterial endothelial dysfunction implicated VEGF-A (vascular endothelial growth factor-A), TGF-β1, angiotensin, and TNFSF12/TWEAK in the injury/remodeling phenotype of PH arterial ECs.
CONCLUSIONS
These data provide high-resolution insights into the complexity and plasticity of the pulmonary endothelium in SSc-associated PH and idiopathic pulmonary arterial hypertension and provide direct molecular insights into soluble mediators and transcription factors driving PH vasculopathy.
PubMed: 38841857
DOI: 10.1161/ATVBAHA.123.320005 -
Frontiers in Cell and Developmental... 2024Skeletal muscle regeneration relies on the intricate interplay of various cell populations within the muscle niche-an environment crucial for regulating the behavior of... (Review)
Review
Skeletal muscle regeneration relies on the intricate interplay of various cell populations within the muscle niche-an environment crucial for regulating the behavior of muscle stem cells (MuSCs) and ensuring postnatal tissue maintenance and regeneration. This review delves into the dynamic interactions among key players of this process, including MuSCs, macrophages (MPs), fibro-adipogenic progenitors (FAPs), endothelial cells (ECs), and pericytes (PCs), each assuming pivotal roles in orchestrating homeostasis and regeneration. Dysfunctions in these interactions can lead not only to pathological conditions but also exacerbate muscular dystrophies. The exploration of cellular and molecular crosstalk among these populations in both physiological and dystrophic conditions provides insights into the multifaceted communication networks governing muscle regeneration. Furthermore, this review discusses emerging strategies to modulate the muscle-regenerating niche, presenting a comprehensive overview of current understanding and innovative approaches.
PubMed: 38840849
DOI: 10.3389/fcell.2024.1385399 -
Neurotherapeutics : the Journal of the... Jun 2024Calcium influx and subsequent elevation of the intracellular calcium concentration ([Ca]) induce contractions of brain pericytes and capillary spasms following...
Calcium influx and subsequent elevation of the intracellular calcium concentration ([Ca]) induce contractions of brain pericytes and capillary spasms following subarachnoid hemorrhage. This calcium influx is exerted through cation channels. However, the specific calcium influx pathways in brain pericytes after subarachnoid hemorrhage remain unknown. Transient receptor potential canonical 3 (TRPC3) is the most abundant cation channel potentially involved in calcium influx into brain pericytes and is involved in calcium influx into other cell types either via store-operated calcium entry (SOCE) or receptor-operated calcium entry (ROCE). Therefore, we hypothesized that TRPC3 is associated with [Ca] elevation in brain pericytes, potentially mediating brain pericyte contraction and capillary spasms after subarachnoid hemorrhage. In this study, we isolated rat brain pericytes and demonstrated increased TRPC3 expression and its currents in brain pericytes after subarachnoid hemorrhage. Calcium imaging of brain pericytes revealed that changes in TRPC3 expression mediated a switch from SOCE-dominant to ROCE-dominant calcium influx after subarachnoid hemorrhage, resulting in significantly higher [Ca] levels after SAH. TRPC3 activity in brain pericytes also contributed to capillary spasms and reduction in cerebral blood flow in an in vivo rat model of subarachnoid hemorrhage. Therefore, we suggest that the switch in TRPC3-mediated calcium influx pathways plays a crucial role in the [Ca] elevation in brain pericytes after subarachnoid hemorrhage, ultimately leading to capillary spasms and a reduction in cerebral blood flow.
PubMed: 38839450
DOI: 10.1016/j.neurot.2024.e00380 -
Adipocyte Dec 2024As a mechanically condensed product of Coleman fat, extracellular matrix/stromal vascular fraction gel (ECM/SVF-gel) eliminates adipocytes, concentrates SVF cells, and... (Comparative Study)
Comparative Study
As a mechanically condensed product of Coleman fat, extracellular matrix/stromal vascular fraction gel (ECM/SVF-gel) eliminates adipocytes, concentrates SVF cells, and improves fat graft retention. This study aims to compare SVF cell composition between Coleman fat and ECM/SVF-gel. Matched Coleman fat and ECM/SVF-gel of 28 healthy women were subjected to RNA-seq, followed by functional enrichment and cell-type-specific enrichment analyses, and deconvolution of SVF cell subsets, reconstructing SVF cell composition in the transcriptome level. ECM/SVF-gels had 9 upregulated and 73 downregulated differentially expressed genes (DEGs). Downregulated DEGs were mainly associated with inflammatory and immune responses, and enriched in fat macrophages. M2 macrophages, resting CD4 memory T cells, M1 macrophages, resting mast cells, and M0 macrophages ranked in the top five most prevalent immune cells in the two groups. The proportions of the principal non-immune cells (e.g., adipose-derived stem cells, pericytes, preadipocytes, microvascular endothelial cells) had no statistical differences between the two groups. Our findings reveal ECM/SVF-gels share the same dominant immune cells beneficial to fat graft survival with Coleman fat, but exhibiting obvious losses of immune cells (especially macrophages), while non-immune cells necessary for adipose regeneration might have no significant loss in ECM/SVF-gels and their biological effects could be markedly enhanced by the ECM/SVF-gel's condensed nature.
Topics: Humans; Female; Extracellular Matrix; Adipose Tissue; Stromal Vascular Fraction; Adult; Macrophages; Adipocytes; Gels; Transcriptome
PubMed: 38829527
DOI: 10.1080/21623945.2024.2360037 -
Cureus May 2024A rare tumor called hemangiopericytoma develops from the pericytes, the cells that surround blood vessels. They frequently grow slowly and might be asymptomatic...
A rare tumor called hemangiopericytoma develops from the pericytes, the cells that surround blood vessels. They frequently grow slowly and might be asymptomatic initially. Although they can develop anywhere in the body, these tumors are most frequently found in the head, pelvis, and legs. This uncommon tumor originates in soft tissues like fat, muscles, tendons, nerves, blood vessels, and other fibrous tissues. The tumor in adolescence can be benign or malignant; it frequently develops in the bones but has the potential to metastasize to the lungs. Imaging tests, such as MRIs or CT scans, are commonly used in diagnosis to determine the location and size of the tumor. We present a case of a 23-year-old male who complained of swelling in his left thigh that had persisted for two years. He underwent multiple biopsies which were inconclusive until wide local excision of the swelling was done. On histopathology, the excised tumor was suggestive of hemangiopericytoma. The patient was advised of radiotherapy for completion of the treatment.
PubMed: 38826872
DOI: 10.7759/cureus.59514 -
Molecules and Cells May 2024Vascular disease, including heart disease, stroke, and peripheral arterial disease, is one of the leading causes of death and disability and represents a significant... (Review)
Review
Vascular disease, including heart disease, stroke, and peripheral arterial disease, is one of the leading causes of death and disability and represents a significant global health issue. Since the development of human induced pluripotent stem cells (hiPSCs) in 2007, hiPSCs have provided unique and tremendous opportunities for studying human pathophysiology, disease modeling, and drug discovery in the field of regenerative medicine. In this review, we discuss vascular physiology and related diseases, the current methods for generating vascular cells (e.g., endothelial cells, smooth muscle cells, and pericytes) from hiPSCs, and describe the opportunities and challenges to the clinical applications of vascular organoids, tissue-engineered blood vessels, and vessels-on-a-chip. We then explore how hiPSCs can be used to study and treat inherited vascular diseases and discuss the current challenges and future prospects. In the future, it will be essential to develop vascularized organoids or tissues that can simultaneously undergo shear stress and cyclic stretching. This development will not only increase their maturity and function but also enable effective and innovative disease modeling and drug discovery.
PubMed: 38825189
DOI: 10.1016/j.mocell.2024.100077