Endothelial cell dysfunction: Implications for the pathogenesis of peripheral artery disease

Kavurma, Mary M.; Bursill, Christina A.; Stanley, Christopher P.; Passam, Freda; Cartland, Siân P.; Patel, Sanjay; Loa, Jacky; Figtree, Gemma A.; Golledge, Jonathan; Aitken, Sarah; Robinson, David

doi:10.3389/fcvm.2022.1054576

Cited by 19 publications

(17 citation statements)

References 190 publications

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“…Although the BM-MNC isolates manufactured in this study fulfilled all quality criteria, BM-MNC isolates manufactured from CLTI patients (REX-001) suffering from type 2 diabetes mellitus may have a different composition and characteristics. Furthermore, the in vitro set-up only involved physiological HUVECs, while in the pathophysiologic situation of patients with CLTI dysfunctional endothelial cells are involved many more cells, chemokines, and inflammatory markers [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Exploring the Effects of Human Bone Marrow-Derived Mononuclear Cells on Angiogenesis In Vitro

Peeters,

Peters,

Videler

et al. 2023

IJMS

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Cell therapies involving the administration of bone marrow-derived mononuclear cells (BM-MNCs) for patients with chronic limb-threatening ischemia (CLTI) have shown promise; however, their overall effectiveness lacks evidence, and the exact mechanism of action remains unclear. In this study, we examined the angiogenic effects of well-controlled human bone marrow cell isolates on endothelial cells. The responses of endothelial cell proliferation, migration, tube formation, and aortic ring sprouting were analyzed in vitro, considering both the direct and paracrine effects of BM cell isolates. Furthermore, we conducted these investigations under both normoxic and hypoxic conditions to simulate the ischemic environment. Interestingly, no significant effect on the angiogenic response of human umbilical vein endothelial cells (HUVECs) following treatment with BM-MNCs was observed. This study fails to provide significant evidence for angiogenic effects from human bone marrow cell isolates on human endothelial cells. These in vitro experiments suggest that the potential benefits of BM-MNC therapy for CLTI patients may not involve endothelial cell angiogenesis.

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Section: Discussionmentioning

confidence: 99%

Exploring the Effects of Human Bone Marrow-Derived Mononuclear Cells on Angiogenesis In Vitro

Peeters,

Peters,

Videler

et al. 2023

IJMS

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“…Differences in sex hormones may also affect arterial compliance, with post-menopausal females having increased arterial stiffness compared to males [13], a finding that is further exaggerated in conditions such as metabolic syndrome [14]. Arterial stiffness contributes to the increased prevalence of hypertension in women [15], and hypertension is a risk factor for PAD [16]. These differences in the biomechanical properties of arteries may affect the sex-dependent outcomes of PAD treatment.…”

Section: Biomechanical Considerationsmentioning

confidence: 99%

Sex, Endothelial Cell Functions, and Peripheral Artery Disease

Cartland,

Stanley,

Bursill

et al. 2023

IJMS

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Peripheral artery disease (PAD) is caused by blocked arteries due to atherosclerosis and/or thrombosis which reduce blood flow to the lower limbs. It results in major morbidity, including ischemic limb, claudication, and amputation, with patients also suffering a heightened risk of heart attack, stroke, and death. Recent studies suggest women have a higher prevalence of PAD than men, and with worse outcomes after intervention. In addition to a potential unconscious bias faced by women with PAD in the health system, with underdiagnosis, and lower rates of guideline-based therapy, fundamental biological differences between men and women may be important. In this review, we highlight sexual dimorphisms in endothelial cell functions and how they may impact PAD pathophysiology in women. Understanding sex-specific mechanisms in PAD is essential for the development of new therapies and personalized care for patients with PAD.

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“…PKG phosphorylates Ca2+-activated K+ channels and inositol trisphosphate receptor-associated cGMP kinase substrates, resulting in a reduction in the cytosolic concentration of Ca2+ and hence the relaxation of vascular smooth muscle cells [ 41 ]. In addition to these biological mechanisms, endothelium derived CNP contributes to maintaining endothelial function and integrity and possibly to the chronic regulation of vascular tone, promoting vasorelaxation in isolated resistance arteries and BP reduction [ 42 , 43 ]. PKG1α plays an important role in the inhibition of inflammation and leukocyte recruitment, platelet aggregation, smooth muscle proliferation, vasoconstriction, fibrosis, coronary microvascular impairment, and hypertrophy through different downstream mechanisms, including SR Ca2+-ATPase (SERCA)-mediated increased re-uptake of Ca2+ into the sarcoplasmic reticulum and the blockade of mitochondrial permeability transition pore [ 44 , 45 ].…”

Section: Natriuretic Peptide Receptorsmentioning

confidence: 99%

Natriuretic Peptides: It Is Time for Guided Therapeutic Strategies Based on Their Molecular Mechanisms

Gallo

Rubattu

Autore

et al. 2023

IJMS

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Natriuretic peptides (NPs) are the principal expression products of the endocrine function of the heart. They exert several beneficial effects, mostly mediated through guanylate cyclase-A coupled receptors, including natriuresis, diuresis, vasorelaxation, blood volume and blood pressure reduction, and regulation of electrolyte homeostasis. As a result of their biological functions, NPs counterbalance neurohormonal dysregulation in heart failure and other cardiovascular diseases. NPs have been also validated as diagnostic and prognostic biomarkers in cardiovascular diseases such as atrial fibrillation, coronary artery disease, and valvular heart disease, as well as in the presence of left ventricular hypertrophy and severe cardiac remodeling. Serial measurements of their levels may be used to contribute to more accurate risk stratification by identifying patients who are more likely to experience death from cardiovascular causes, heart failure, and cardiac hospitalizations and to guide tailored pharmacological and non-pharmacological strategies with the aim to improve clinical outcomes. On these premises, multiple therapeutic strategies based on the biological properties of NPs have been attempted to develop new targeted cardiovascular therapies. Apart from the introduction of the class of angiotensin receptor/neprilysin inhibitors to the current management of heart failure, novel promising molecules including M-atrial natriuretic peptide (a novel atrial NP-based compound) have been tested for the treatment of human hypertension with promising results. Moreover, different therapeutic strategies based on the molecular mechanisms involved in NP regulation and function are under development for the management of heart failure, hypertension, and other cardiovascular conditions.

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Endothelial cell dysfunction: Implications for the pathogenesis of peripheral artery disease

Cited by 19 publications

References 190 publications

Exploring the Effects of Human Bone Marrow-Derived Mononuclear Cells on Angiogenesis In Vitro

Exploring the Effects of Human Bone Marrow-Derived Mononuclear Cells on Angiogenesis In Vitro

Sex, Endothelial Cell Functions, and Peripheral Artery Disease

Natriuretic Peptides: It Is Time for Guided Therapeutic Strategies Based on Their Molecular Mechanisms

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