Contemporary Medical Management of Peripheral Arterial Disease

Cook, Ian O.; Chung, Jayer

doi:10.1007/s10557-023-07516-2

Cited by 2 publications

(1 citation statement)

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“…The novel role of PLXND1 and KLF2 as vascular caliber regulators suggests that variants in these genes could contribute to diseases involving reduced vascular calibers, myocardial ischemia [173,174], peripheral artery disease [175], atherosclerosis [29], hypertension [176], diabetes [177], and glaucoma [178]. Thus, increasing the expression or activity of Plexin D1 and KLF2 might therapeutically enhance the blood flow in individuals afflicted by these conditions and in patients with congenital heart defects suffering from impaired cardiac blood flow.…”

Section: Discussionmentioning

confidence: 99%

Plxnd1-mediated mechanosensing of blood flow controls the caliber of the Dorsal Aorta via the transcription factor Klf2

He,

Blazeski,

Nilanthi

et al. 2024

Preprint

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The cardiovascular system generates and responds to mechanical forces. The heartbeat pumps blood through a network of vascular tubes, which adjust their caliber in response to the hemodynamic environment. However, how endothelial cells in the developing vascular system integrate inputs from circulatory forces into signaling pathways to define vessel caliber is poorly understood. Using vertebrate embryos and in vitro-assembled microvascular networks of human endothelial cells as models, flow and genetic manipulations, and custom software, we reveal that Plexin-D1, an endothelial Semaphorin receptor critical for angiogenic guidance, employs its mechanosensing activity to serve as a crucial positive regulator of the Dorsal Aorta's (DA) caliber. We also uncover that the flow-responsive transcription factor KLF2 acts as a paramount mechanosensitive effector of Plexin-D1 that enlarges endothelial cells to widen the vessel. These findings illuminate the molecular and cellular mechanisms orchestrating the interplay between cardiovascular development and hemodynamic forces.

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Section: Discussionmentioning

confidence: 99%

Plxnd1-mediated mechanosensing of blood flow controls the caliber of the Dorsal Aorta via the transcription factor Klf2

He,

Blazeski,

Nilanthi

et al. 2024

Preprint

View full text Add to dashboard Cite

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Genetic support of the causal association between gut microbiota and peripheral artery disease: a bidirectional Mendelian randomization study

Shi,

Yuan,

et al. 2024

Aging

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Background: The causal relationship between gut microbiota and peripheral artery disease (PAD) is still not clear. In this research, we employed the Mendelian randomization (MR) technique to explore the potential causal connection between 211 gut microbiota species and PAD. We also investigated whether the causal effects operate in both directions. Methods: We used Genome-wide Association Studies (GWAS) summary statistics data from the MiBioGen and FinnGen consortia to conduct a two-sample MR analysis to explore the causal link between gut microbiota and PAD. Sensitivity analysis is conducted to assess the robustness of the MR results. In addition to that, reverse MR analysis was performed to examine the inverse causal relationship. Results: The inverse variance weighted (IVW) method provided evidence supporting a causal relationship between 9 specific gut microbiota taxa and PAD. The study findings indicated that family Family XI (OR=1.

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Contemporary Medical Management of Peripheral Arterial Disease

Cited by 2 publications

References 100 publications

Plxnd1-mediated mechanosensing of blood flow controls the caliber of the Dorsal Aorta via the transcription factor Klf2

Plxnd1-mediated mechanosensing of blood flow controls the caliber of the Dorsal Aorta via the transcription factor Klf2

Genetic support of the causal association between gut microbiota and peripheral artery disease: a bidirectional Mendelian randomization study

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