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Investigation Of Inflammation And Apoptosis Mediated Toxicity In Response To Metal Oxide Nanoparticles In Ml-1 And Ca77 Cancer Cell Lines, Alyse N. Peters Jan 2023

Investigation Of Inflammation And Apoptosis Mediated Toxicity In Response To Metal Oxide Nanoparticles In Ml-1 And Ca77 Cancer Cell Lines, Alyse N. Peters

MSU Graduate Theses

Metal oxide nanoparticles (MONPs) are becoming more popular in today’s environment. They contribute significantly to the technologies in agriculture and food development but there is little understanding to how MONPs, including ZnO, CuO, TiO2, and SnO2, impact human health and the environment. Our growth assay revealed that none of these negatively affects viability in the budding yeast, Saccharomyces cerevisiae. In contrast, both human thyroid cancer cells (ML-1) and rat medullary thyroid cancer cells (CA77) displayed a significant reduction in viability with the treatment of CuO and ZnO. The production of ROS in these cell lines when treated with CuO and …


Sex-Dependent Effects Of Induced Acute Inflammation On Glucose Homeostasis And Rna Editing Enzymes, Christian A. Rivas Jan 2023

Sex-Dependent Effects Of Induced Acute Inflammation On Glucose Homeostasis And Rna Editing Enzymes, Christian A. Rivas

MSU Graduate Theses

The first line of defense against bodily insults, like pathogen invasion, is the innate immune system. Innate immunity sets in motion countless cascades that result in inflammation. Inflammation simultaneously affects multiple biological processes like metabolism and gene expression. Males and females react differently to inflammation. To understand both molecular and physiological sex differences in inflammation, we examined how inflammation affects gene expression and glucose metabolism. Adenosine deaminase acting on RNA (ADAR1) is upregulated by inflammation and catalyzes RNA editing, a process where nucleotides encoded by the genome are modified. ADAR1 also controls the innate immune reaction by decreasing activity of …


Cul3 Negatively Regulates Nlrp12-Mediated Inhibition Of The Canonical Nf-Κb Signaling Pathway, Inyeong Lee Jan 2023

Cul3 Negatively Regulates Nlrp12-Mediated Inhibition Of The Canonical Nf-Κb Signaling Pathway, Inyeong Lee

MSU Graduate Theses

Nod-like receptor family pyrin domain-containing protein 12 (NLRP12) is mainly known for its inhibitory function on NF-κB signaling in innate immune cells, and more recently, for its ability to regulate chemokine signaling and ubiquitination of the immune receptor RIG-I. Through a yeast 2-hybrid screen, the Lupfer lab previously discovered that NLRP12 interacts with other ubiquitin-associated proteins including Cullin 3 (CUL3) and RING finger protein 2 (RNF2). This research was conducted to mainly investigate the interaction between NLRP12 and CUL3 in human cells and examine the role in regulating NF-κB signaling. Previously, co-immunoprecipitation, followed by western blot analysis, and confocal microscopy …


Identification Of A Novel Protein Interaction That Elucidates The Mechanism Of Idiopathic Recurrent Miscarriages In Women With Nlrp2 Mutations, Nayeon Son Jan 2022

Identification Of A Novel Protein Interaction That Elucidates The Mechanism Of Idiopathic Recurrent Miscarriages In Women With Nlrp2 Mutations, Nayeon Son

MSU Graduate Theses

The protein NOD-Like receptor pyrin domain containing 2 (NLRP2) is one member of a larger family of protein receptors that plays an important role in our innate immune system. In humans, the NLR family consists of 22 proteins. However, only about a half of NLRs’ functions are known, but many are pro-inflammatory, causing inflammation. NLRP2 has been identified to be a maternal effect gene regulating early embryo development in idiopathic recurrent miscarriages. In previous studies, mutations in the NLRP2 gene resulted in genetic maternal imprinting disorders due to NLRP2 regulating DNA methylation. However, the exact mechanisms involved in recurrent miscarriages …


Analysis Of Root System Architecture And Qtl Identification In Grapevines, Sujan Thapa Jan 2022

Analysis Of Root System Architecture And Qtl Identification In Grapevines, Sujan Thapa

MSU Graduate Theses

The root system of the plant plays a vital role in water and nutrient uptake. Native North American grapevines adapted to a broad range of climatic and soil conditions, which led to the evolution of diverse root system architecture (RSA) within the Vitis genus. Despite the importance of RSA in viticulture, little is known about the genetic basis of the RSA in grapevine. I used novel root phenotyping tool, RhizoVision Analyzer to characterize the root system of 208 genotypes of an F1 grapevine progeny obtained from a cross between Vitis rupestris Scheele B38 and Vitis riparia Michx. HP-1. Dormant …


Tissue And Sex-Specific Rna Editing During Induced Acute Inflammation, Claire E. Nichols Jan 2022

Tissue And Sex-Specific Rna Editing During Induced Acute Inflammation, Claire E. Nichols

MSU Graduate Theses

A-to-I RNA editing is a process where select adenosine (A) nucleotides are deaminated by an editing enzyme, ADAR, to become inosines (I) in RNA transcripts. RNA editing can affect the sequence of the encoded protein and the regulation of the RNA. ADAR1 also plays a role in regulating innate immunity and its expression is upregulated during inflammation. Current data on the effects of increasing ADAR1 on RNA editing is limited, and most studies are completed only in male animals. We are interested in expanding RNA editing data to include female animals. Lipopolysaccharide (LPS) was used to induce acute inflammation and …


Further Investigation Of The Initiating Mechanism Of The Type I Collagen Glomerulopathy, Matthew James Freese Jan 2022

Further Investigation Of The Initiating Mechanism Of The Type I Collagen Glomerulopathy, Matthew James Freese

MSU Graduate Theses

The progressive accumulation of collagen and other extracellular matrix proteins in the renal mesangium results in fibrosis, glomerulosclerosis, and eventual renal failure. Mice deficient in integrating α2(I) collagen into the type I collagen structure, termed Col1a2-deficient mice, model kidney fibrosis through the condition Type I Collagen Glomerulopathy, because homotrimeric type I collagen accumulates extracellularly in the mesangium of renal glomeruli. Accumulation of homotrimeric type I collagen compresses blood vessels in glomeruli, which reduces filtration, increases pressure, and results in fibrosis. Picrosirius red (PSR) staining was used on Col1a2 deficient and wildtype mice to evaluate collagen deposition. Histological evaluation and …


Elucidating The Role Of Hemodynamic Force In Regulating The Attachment Of Vascular Smooth Muscle Cells (Vsmcs) To Maturing Vessels During Mouse Embryonic Development, Israt Jahan Jan 2022

Elucidating The Role Of Hemodynamic Force In Regulating The Attachment Of Vascular Smooth Muscle Cells (Vsmcs) To Maturing Vessels During Mouse Embryonic Development, Israt Jahan

MSU Graduate Theses

Blood vessel maturation is characterized by the recruitment and attachment of vascular smooth muscle cells (vSMCs) around immature blood vessels, which ultimately form the tunica media. Improper maturation can lead to vascular birth defects ranging from minor birthmarks to lethal brain aneurysms. Previously, our lab demonstrated that hemodynamic force plays an important role to regulate vSMCs recruitment from neighboring low-flow to high-flow vessels followed by the attachment of these vSMCs to the high-flow vessels. To understand the reason for the preferred attachment of vSMCs to high-flow vessels, instead of low-flow vessels, I hypothesize that hemodynamic force modulates the expression of …


A Study Of Cobalt (Iii) Oxide Nanoparticle Delivery Of Sirna Molecules Directed Against Signaling Intermediates Of The P2y2 Receptor, Rachel Blair Stroud Jan 2022

A Study Of Cobalt (Iii) Oxide Nanoparticle Delivery Of Sirna Molecules Directed Against Signaling Intermediates Of The P2y2 Receptor, Rachel Blair Stroud

MSU Graduate Theses

G protein-coupled receptors are evolutionarily ubiquitous sensors of extracellular signals, propagating intracellular signal cascades through heterotrimeric G proteins. P2Y2 receptors are GPCRs which are activated by extracellular nucleotides to mediate signaling cascades via Gαq coupling. Many GPCRs are subject to a common mechanism for signal termination involving phosphorylation of the C-terminal tail followed by β-arrestin binding and subsequent endocytic internalization of the complex. This effect has been described for the P2Y2 R in the 1321N1 astrocytoma cell line, and UTP-induced activation and desensitization profiles have been previously defined. There is need to develop molecular vehicles for safe and …


An Assessment Of Inp/Zns As Potential Anti-Cancer Therapy: Quantum Dot Treatment Induces Stress On Hela Cells, Victoria Grace Davenport Aug 2021

An Assessment Of Inp/Zns As Potential Anti-Cancer Therapy: Quantum Dot Treatment Induces Stress On Hela Cells, Victoria Grace Davenport

MSU Graduate Theses

Indium Phosphide/Zinc Sulfide (InP/ZnS) quantum dots (QDs) are an emerging option in QD technologies for uses of fluorescent imaging as well as targeted drug and anti-cancer therapies based on their customizable properties. In this study we explored effects of InP/ZnS when treated with HeLa cervical cancer cells. We employed XTT viability assays, reactive oxygen species (ROS) analysis, and apoptosis analysis to better understand cytotoxicity extents at different concentrations of InP/ZnS. In addition, we compared the transcriptome profile from the QDtreated HeLa cells with that of untreated HeLa cells to identify changes to the transcriptome in response to the QD. Intracellular …


Nucleotide P2y₂ Receptor-Dependent Leukocyte-Endothelial Interaction, Spencer E. Thomas Aug 2021

Nucleotide P2y₂ Receptor-Dependent Leukocyte-Endothelial Interaction, Spencer E. Thomas

MSU Graduate Theses

Extracellular nucleotides (ATP, UTP) released from cells act on nucleotide receptors to promote vascular inflammation. Increased leukocyte-endothelial interaction is a hallmark of vascular inflammation. The nucleotide P2Y₂ receptor (P2Y₂R), activated by extracellular ATP≈UTP, plays a role in cardiovascular homeostasis and immune regulation. Moreover, accumulating evidence from studies in vitro and in vivo models have implicated the P2Y₂R in the inflammatory response significantly contributing to the progression and pathogenesis of asthma, atherosclerosis, sepsis, and ischemia. I hypothesized that P2Y₂R activation by UTP, an agonist of the receptor, increased leukocyte rolling and adhesion in the microvasculature from baseline. To test the hypothesis, …


Neuronal Migration In Developmental Hyperserotonmia: Assessment Of Vesicular Glutamate In The Raphe Nuclei, Trey M. Shupp Aug 2021

Neuronal Migration In Developmental Hyperserotonmia: Assessment Of Vesicular Glutamate In The Raphe Nuclei, Trey M. Shupp

MSU Graduate Theses

The neurotransmitter serotonin is involved in the early development of the central nervous system and the organization of neurons throughout the cerebral cortex and cerebellum. It is proposed that serotonin indirectly interacts with cells in the marginal zone of the cerebral cortex known as Cajal-Retizus (CR) cells. These cells secrete the extracellular matrix protein reelin, which is known for its role in neuronal organization and migration during early neural development. It has been observed that low levels of serotonin are associated with similarly low levels of reelin during development and have been reported to result in disorganization of neurons in …


Investigating Chitosan Modified With Triethylammonium Butanamide And Triethylphosphonium Butanamide As Non-Viral Gene Delivery Vectors By Examining Cytotoxicity And Transfection Efficiency, Deborah C. Ehie Aug 2020

Investigating Chitosan Modified With Triethylammonium Butanamide And Triethylphosphonium Butanamide As Non-Viral Gene Delivery Vectors By Examining Cytotoxicity And Transfection Efficiency, Deborah C. Ehie

MSU Graduate Theses

Gene therapy is a very challenging field, especially with new emerging genetic disorders. Chitosan (CS), due to chitosan’s flexibility, biocompatibility, and biodegradability, has been of interest in the world of gene therapy especially as researchers are gravitating towards non-viral vectors due to the problems caused by viral vectors. Nevertheless, there are still issues regarding solubility, cellular uptake of cargos being transported in vitro or in vivo, increased cytotoxicity levels, as well as many other things that prevent chitosan from being an efficient gene delivery agent. Here I present five derivatives of chitosan, which were all modified with either triethylphosphonium …


Myosin V-Mediated Cargo Traffic Toward The Trans-Golgi Network And Myosin V Implications In Snc1 Exocytosis, Vy Ngoc Khanh Nguyen May 2020

Myosin V-Mediated Cargo Traffic Toward The Trans-Golgi Network And Myosin V Implications In Snc1 Exocytosis, Vy Ngoc Khanh Nguyen

MSU Graduate Theses

Retrieval of cargo proteins from the endosome towards the trans-Golgi network (TGN) is a crucial intracellular process for cellular homeostasis. Its dysfunction is associated with pathogenesis of Alzheimer and Parkinson's diseases. Myosin family proteins are cellular motors walking along actin filaments by utilizing the chemical energy from ATP hydrolysis, known to involve in pleiotropic cellular trafficking pathways. However, the question of whether myosins play a role in the trafficking of Snc1 and Vps10 has not been addressed yet. The present study assesses the potential roles of all five yeast myosins in the recycling of two membrane cargo, Snc1 and …


A Novel Uv Resistance In Rad23-Depleted Tetrahymena Thermophila, Emily M. Schmoll May 2020

A Novel Uv Resistance In Rad23-Depleted Tetrahymena Thermophila, Emily M. Schmoll

MSU Graduate Theses

Rad23 is a highly conserved cellular scaffold protein which participates in the nucleotide excision repair pathway and ubiquitin proteasome system. It is hypothesized that the contradictory roles of Rad23 within these two systems, acting to enhance stability or facilitate degradation respectively, could be regulated via post-translational modification of the ubiquitin-like domain of the protein. To this end, a Rad23 somatic knockout cell line was established in Tetrahymena thermophila, with the eventual goal of knocking in a mutant Rad23 protein lacking potential for UbL ubiquitylation. In contrast to the UV-sensitive phenotype observed in similar models, Rad23-depleted Tetrahymena cell lines displayed significantly …


Elucidating The Developmental Defects In Zebrafish Associated With The Cardiac Drug Verapamil, Blake Stephan Justis May 2020

Elucidating The Developmental Defects In Zebrafish Associated With The Cardiac Drug Verapamil, Blake Stephan Justis

MSU Graduate Theses

Birth defects are abnormalities in a developing organism that lead to a malformation in structure or function. Over half of birth defects have no determined cause; however, known causes occur by genetic anomalies, exposure to environmental agents (a.k.a. teratogens), or multifactorial reasons. To explain the unknown causes of birth defects, an area of focus in this study is to identify potential teratogens. Identifying these teratogens, is key to preventing future birth defects. An obvious source of teratogens in pregnant women would be that of pharmaceuticals. Thus, a main goal of this study is to identify drugs that cause birth defects. …


Cyclophilin A Enhances Hiv-1 Reverse Transcription In Human Microglial Cells, Zachary Michael Ingram Dec 2019

Cyclophilin A Enhances Hiv-1 Reverse Transcription In Human Microglial Cells, Zachary Michael Ingram

MSU Graduate Theses

Parenchymal microglia represent a susceptible cell type to HIV infection and contribute to HIV Associated Neurocognitive Disorders (HAND). Currently, HIV host-protein interactions in microglia are understudied, but relevant to the design of antiviral drugs. HIV replication events rely on host and viral proteins to evade an immune response while improve replication success. Post-fusion the HIV capsid is released into the cytoplasm and begins trafficking towards the nucleus. During transit viral RNA is transcribed to DNA through reverse transcription (RT). In addition, the HIV capsid that protects the reverse transcription complex disassembles in a step termed uncoating. Once the pre-integration complex …


Towards A Better Understanding Of Temporomandibular Disorder, Jessica R. Cox May 2019

Towards A Better Understanding Of Temporomandibular Disorder, Jessica R. Cox

MSU Graduate Theses

Results from the OPPERA study provided evidence that risk factors such as neck muscle tension, prolonged jaw opening, and female gender increase the likelihood of developing temporomandibular joint disorders (TMJD), which are prevalent, debilitating orofacial pain conditions. Peripheral and central sensitization, which mediate a lowering of the stimulus required for pain signaling, are implicated in the underlying pathology of chronic TMJD. The goal of my study was to investigate cellular changes in the expression of proteins associated with the development of central sensitization. Female Sprague-Dawley rats were injected with complete Freund’s adjuvant in the upper trapezius muscles to promote trigeminal …


Further Characterization Of The Skeletal Phenotype In A Hurler Syndrome Mouse Model And The Ethical Treatment Of Children In Medicine, Anna Marie Mcwoods May 2019

Further Characterization Of The Skeletal Phenotype In A Hurler Syndrome Mouse Model And The Ethical Treatment Of Children In Medicine, Anna Marie Mcwoods

MSU Graduate Theses

Mucopolysaccharidosis type I (MPS I) is a rare, autosomal recessive disorder caused by the deficiency of the lysosomal enzyme α-L-iduronidase (IDUA). Absence of IDUA results in the accumulation of dermatan and heparin sulfate and ultimately causes multi-system dysfunction. The most severe form of MPS I is Hurlers syndrome, a rapidly progressive disorder that, if left untreated, is fatal. Current treatment options for diagnosed individuals includes hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT). These treatments are able to ameliorate the majority of symptoms with the exception of the bone phenotype. This investigation aimed to further characterize the bone …


Kinetics Of Hiv-1 Uncoating In C20 Microglial Cells, Melanie Anne Taylor May 2019

Kinetics Of Hiv-1 Uncoating In C20 Microglial Cells, Melanie Anne Taylor

MSU Graduate Theses

Uncoating is a poorly understood yet required step of HIV-1 replication that is defined as the disassembly of the viral capsid structure. The goal of this project is to characterize uncoating in C20 microglial cells. These cells are a natural target of HIV-1 that are infected to establish latent viral reservoirs and HIV-associated neurological disorders. A stable C20 cell line that expresses TRIM-CypA was established to study the kinetics of uncoating with the CsA washout assay. The expression of TRIM-CypA was confirmed by western blot and the functionality of the protein was confirmed by a viral infectivity assay. Using this …


Effects Of Herbicides On Zebrafish Embryo Development And Viability, Kayla Ray King May 2019

Effects Of Herbicides On Zebrafish Embryo Development And Viability, Kayla Ray King

MSU Graduate Theses

Environmental contaminants are chemicals of anthropogenic origin that are found in water, soil, and air, and are harmful to a wide variety of organisms (ORD US EPA, 2018-a). One common group of contaminants are herbicides. Though herbicides are used to control unwanted vegetation in agriculture, aquatic organisms and humans may be exposed to these herbicides through run off into streams and rivers, by drinking contaminated water, by consuming treated crops, by direct exposure, or through bioaccumulation. Thus the effect of these herbicides on animals needs further investigation. In this study, I sought to determine whether six different herbicides, which have …


The Role Of Rad4 In Dna Repair And Its Interplay With Telomeres In Tetrahymena Thermophila, Emily Nischwitz Aug 2018

The Role Of Rad4 In Dna Repair And Its Interplay With Telomeres In Tetrahymena Thermophila, Emily Nischwitz

MSU Graduate Theses

Telomeres are repetitive parts of the genome that act as a protective end cap to the chromosomes. Telomeres are critical to the integrity and stability of the genome, therefore, ensuring that their sequence is maintained, even after damage, is crucial. Much of the pioneering work responsible for explaining telomeres has been conducted in ciliates, specifically in Tetrahymena thermophila. Telomeres in T. thermophila have a high amount of tandem thymine repeats (GGGGTT) and, thus, are susceptible to ultraviolet light (UV) induced lesions called pyrimidine dimers, which must be repaired by nucleotide excision repair (NER). In humans, Xeroderma Pigmentosum C (XPC) …


Low Hemodynamic Loading Alters Heart Morphogensis In E8.5 To E9.5 Mouse Embryos, Tanner Gerard Hoog May 2018

Low Hemodynamic Loading Alters Heart Morphogensis In E8.5 To E9.5 Mouse Embryos, Tanner Gerard Hoog

MSU Graduate Theses

Hemodynamic loading, the force exerted on the cardiovascular walls as blood circulates, has been shown to alter heart morphology in chick and zebrafish embryos, but has yet to be shown to singly influence mouse heart development. Defects of heart morphology found in model organisms with physically altered hemodynamics resemble the aberrations seen in human congenital heart disease and are therefore crucial to understand in a mammalian model. In the present study, hemodynamic loading was altered by lowering the hematocrit of early stage mouse embryos. This was accomplished by injecting acrylamide and TEMED into the blood islands of cultured embryos to …


Investigation Of The Homologs Rad51 And Dmc1 Role In Cell Division And Homologous Recombination, Amaal Abulibdeh May 2018

Investigation Of The Homologs Rad51 And Dmc1 Role In Cell Division And Homologous Recombination, Amaal Abulibdeh

MSU Graduate Theses

RecA-like proteins homologs Rad51 and Dmc1 (disruption of meiotic control) promote recombination between homologous chromosomes by repairing programmed DNA Double-Strand Breaks (DSBs). Dmc1 is a Recombinase involved in meiosis-specific repair of DSBs, whereas Rad51 has been found to be involved in meiotic and non-meiotic DSBs repair. Previous studies showed that when RAD51 is overexpressed, interhomologous recombination still occurs even when DMC1 is knocked out. Dmc1 and Rad51 have not been fully characterized in the ciliate Tetrahymena thermophila. In order to more fully investigate the role of Rad51 and Dmc1 in Homologous Recombination Repair (HHR), this work focuses on using …


Development Of Endogenous Tagging Plasmids For Characterization Of Protein Interactions, Localization, And Post-Translational Modifications Of Tetrahymena Thermophila Rad23, Evan Andrew Wilson May 2018

Development Of Endogenous Tagging Plasmids For Characterization Of Protein Interactions, Localization, And Post-Translational Modifications Of Tetrahymena Thermophila Rad23, Evan Andrew Wilson

MSU Graduate Theses

Rad23 is a protein involved in both nucleotide excision repair (NER) and proteasome-mediated degradation, and has been suggested to facilitate interactions between these two pathways. The model organism Tetrahymena thermophila, which has a transcriptionally silent micronucleus, provides a useful platform for studying the role of Rad23 in global genome NER (GG-NER). However, the ectopic expression systems used thus far in T. thermophila to study Rad23 are repressed by UV light and do not account for the background expression of endogenous RAD23; these phenomena prevent insightful gains to the true dynamics of Rad23. In this thesis, endogenous tagging …


Yeast Dynamin And Ypt6 Converge On The Garp For Endosome-To-Golgi Trafficking, Pelin Makaraci Dec 2017

Yeast Dynamin And Ypt6 Converge On The Garp For Endosome-To-Golgi Trafficking, Pelin Makaraci

MSU Graduate Theses

Protein recycling is an important cellular process required for cell homeostasis. Results from prior studies demonstrated that Vps1, a dynamin homologue in yeast, is implicated in protein recycling from the endosome to the trans-Golgi Network (TGN). However, the function of Vps1 in relation to Ypt6, a master GTPase in the recycling pathway, remains unknown. The present study reveals that Vps1 physically interacts with Ypt6 if at least one of them is full-length. It was found that overexpression of full-length Vps1, but not GTP hydrolysis-defective Vps1 mutants, is sufficient to rescue abnormal phenotypes in membrane trafficking pathways provoked by loss …


The Role Of Hemodynamic Force On Development Of The Mouse Embryonic Heart, Samantha Jean Fredrickson Aug 2017

The Role Of Hemodynamic Force On Development Of The Mouse Embryonic Heart, Samantha Jean Fredrickson

MSU Graduate Theses

The most common type of birth defects are congenital heart defects (or CHDs). Though a few cases of CHDs have been attributed to genetic defects specific to the heart, substance exposure, or to maternal disease, the cause of most CHDs is unknown. Thus, further research is needed to determine how CHDs form. Very few studies have investigated how physiological factors like perturbations of blood flow can affect normal heart development. For instance, increasing or decreasing the resistance to blood flow can alter development of the heart in both zebrafish and chicken embryos. This could be one mechanism to explain CHD …


The Effect Of Hemodynamic Force On The Maturation Of Blood Vessels During Embryogenesis, Rachel Lee Padget Aug 2017

The Effect Of Hemodynamic Force On The Maturation Of Blood Vessels During Embryogenesis, Rachel Lee Padget

MSU Graduate Theses

Throughout embryonic development, blood vessels are derived from endothelial cells by way of vasculogenesis. During angiogenesis, vessels remodel to form a hierarchy of large-diameter arteries that branch into small-diameter capillaries. In this maturation, vessels respond to unidentified signaling events to become surrounded with an outer layer of vascular smooth muscle cells (vSMCs). This results in arteries that have a thick vSMC layer, veins that have a thin vSMC layer, and capillaries that have a very thin or absent vSMC layer. What remains to be determined is the cause of the thicker layer of vSMCs around proximal arteries. Previous studies …