Browsing by Author "Jiang, Yizhi"

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    Expression of Nuclear Lamin Proteins in Endothelial Cells is Sensitive to Cell Passage and Fluid Shear Stress
    (Springer, 2018-02) Jiang, Yizhi; Ji, Julie Y.; Engineering Technology, School of Engineering and Technology
    Introduction Vascular cells are regulated by continuous hemodynamic forces in vivo, and mechanical forces such as shear stress are proposed to involve in the progression of cardiovascular diseases such as atherosclerosis. Lamin A/C makes up the nuclear lamina, which structurally supports the nucleus while also functionally participates in chromatin organization and gene transcription. Diseases caused by lamin or other nuclear proteins are called laminopathies. One example, Hutchinson Gilford Progeria Syndrome (HGPS) where young patients show signs of accelerated aging, is caused by de novo mutations on the lamin A/C gene. Vasculature of HGPS patients shares many similarities with people of advanced age, suggesting a role for lamin in vascular aging. Methods In this study, we examined how arterial shear stress affects lamin A/C expression in bovine aortic endothelial cells at different population doubling levels (PDL). We also used fluorescence image analysis to examine nuclear shape changes with shear stress and PDL. Results Our results suggest that laminar shear stress downregulated lamin A/C expression in low PDL cells, but the effect was reversed in high PDL cells. Nuclear shape changes were more prominent after shear stress in low PDL cells. Moreover, lamin A/C accumulated more at the nuclear periphery after exposure to shear stress. Conclusions Overall, our results indicate that both shear stress and cell passage can have an impact on lamin expressions at transcriptional and translational levels, as we continue to understand the effect of shear stress on endothelial lamina as part of the vascular aging process.
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    Mechano-sensitivity of nuclear lamin proteins in endothelial cells
    (2016-07-22) Jiang, Yizhi; Ji, Julie Ying Hui; Na, Sungsoo; Wallace, Joseph
    Atherosclerosis is a chronic disease that happens mostly in aged people, and recently studies have showed many similarities between Hutchinson Gilford Progeria Syndrome (HGPS) cells and aging cells, implicating dysfunctions of lamin A/C in aging process and atherosclerosis, as HGPS is caused by a mutated form of lamin A/C. Blood flow in arteries is generating shear stress that is mostly applied on endothelial cells that align along inner blood vessel wall. At the same time, endothelial cells are also under stretch by periodic arterial pulses. Considering the fact that atherosclerosis is prone to developing at arterial branches with disturbed shear and increased stretch, it is highly possible that laminar flow and proper stretch force are regulating endothelium to function appropriately. In this thesis, the investigation of what effects laminar flow or cyclic stretch can bring to endothelial cells was conducted, and examination of lamin A/C expression under mechanical forces were elaborated and incorporated with cell senescence. Results showed that laminar shear stress and stretch force can regulate lamin A/C expression in different patterns, which were impaired in senescent cells.
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    Passage dependent changes in nuclear and cytoskeleton structures of endothelial cells under laminar shear stress or cyclic stretch
    (Medip Academy, 2021) Jiang, Yizhi; Witt, Nathaniel; Ji, Julie Y.; Biomedical Engineering, Purdue School of Engineering and Technology
    Background: The ability of vascular endothelium to sense and respond to the mechanical stimuli generated by blood flow is pivotal in maintaining arterial homeostasis. A steady laminar flow tends to provide athero-protective effect via regulating endothelial functions, vascular tone, and further remodeling process. As arterial aging appeared to be an independent risk factor of cardiovascular diseases, it is critical to understand the effects of cell senescence on endothelial dysfunction under dynamic mechanical stimuli. Methods: In this study, we investigated the morphological responses of aortic endothelial cells toward laminar flow or cyclic stretch. Automated image recognition methods were applied to analyze image data to avoid bias. Differential patterns of morphological adaptations toward distinct mechanical stimuli were observed, and the shear-induced changes were found to be more associated with cell passages than that of cyclic strain. Results: Our results demonstrated that the cytoskeleton and nuclear structural adaptations in endothelial cells toward laminar flow were altered over prolonged culture, suggesting that the failure of senescent endothelial cells to adapt to the applied shear stress morphologically could be one of the contributors to endothelial dysfunctions during vascular aging. Conclusions: Results indicated that cells were able to adjust their cytoskeleton and nuclear alignment and nuclear shapes in response to the applied mechanical stimuli, and that the shear-induced changes were more dependent on PD levels, where cells with higher PDL were more responsive to external forces.
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    Progerin-Induced Impairment in Wound Healing and Proliferation in Vascular Endothelial Cells
    (Frontiers Media, 2022-03-14) Jiang, Yizhi; Ji, Julie Y.; Biomedical Engineering, Purdue School of Engineering and Technology
    Progerin as a mutated isoform of lamin A protein was first known to induce premature atherosclerosis progression in patients with Hutchinson-Gilford progeria syndrome (HGPS), and its role in provoking an inflammatory response in vascular cells and accelerating cell senescence has been investigated recently. However, how progerin triggers endothelial dysfunction that often occurs at the early stage of atherosclerosis in a mechanical environment has not been studied intensively. Here, we generated a stable endothelial cell line that expressed progerin and examined its effects on endothelial wound repair under laminar flow. We found decreased wound healing rate in progerin-expressing ECs under higher shear stress compared with those under low shear. Furthermore, the decreased wound recovery could be due to reduced number of cells at late mitosis, suggesting potential interference by progerin with endothelial proliferation. These findings provided insights into how progerin affects endothelial mechanotransduction and may contribute to the disruption of endothelial integrity in HGPS vasculature, as we continue to examine the mechanistic effect of progerin in shear-induced endothelial functions.
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    Understanding lamin proteins and their roles in aging and cardiovascular diseases
    (Elsevier, 2018-11) Jiang, Yizhi; Ji, Julie Y.; Biomedical Engineering, School of Engineering and Technology
    The occurrence of cardiovascular diseases increases with age independent of other risk factors, and the percentage of senescent cells is significantly elevated in vascular cells at atherosclerotic sites. Patients with accelerated aging syndromes caused by mutant lamin A protein, a structural component in nuclear lamina, also share many similarities with normal aged people, including the propensity to develop atherosclerosis. Recent studies have revealed the accumulation of prelamin A in normal aged vascular cells, and that lamin A participated as a mechanosensitive molecule in regulating various cellular events. These findings suggest that the ectopic expression of mutant lamin A or lamin A precursor (prelamin A) not only causes defects in cell mechanics, but it also disturbs stress-induced mechanotransduction pathways involving lamin A, both of which may contribute to vascular dysregulation. This review summarizes the current understanding of how lamin proteins are involved in vascular cell during aging, with a particular focus on the effect of mechanical stresses from blood flow on nuclear lamina of endothelial cells. Related studies are clarifying the role of lamin A in the progression of atherosclerosis, which will aid in the development of potential therapies for those suffering from lamin A-associated accelerated aging syndromes.