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One of the potential causes of hypertension is endothelial dysfunction associated with a decreased production of the vasodilator nitric oxide (NO). Possible factors which may contribute to the reduced NO production include increased reactive oxygen species (eg. superoxides); increased concentrations of homocysteine; or decreased concentrations of L-arginine (cationic amino acids). L-arginine, the precursor of NO, not only increases the bioavailability of NO by increasing its production; but also by reducing the inactivation of NO by superoxides. In patients with hypertension, although fasting plasma L-arginine concentrations are elevated, L-arginine supplementation has been shown to decrease blood pressure. A possible explanation for these data may be that L-arginine uptake into cells is impaired and therefore would not be available for NO production. Indeed, studies have shown that cellular uptake of L-arginine is reduced in lymphocytes from patients with hypertension and individuals genetically predisposed to developing hypertension. However, elucidating the kinetics of L-arginine uptake into endothelial cells is fundamental to determine whether L-arginine uptake is indeed impaired. Previous studies have shown that the uptake of cationic amino acids into endothelial cells is mediated by the high affinity/low rate y+L transporter and the low affinity/high rate y+ transporter. However, data on the kinetics, the relative contribution and physiological importance of the individual transporters in cells expressing more than one transporter, are inconsistent; as most studies determining the uptake of radiolabelled amino acids have assumed Michaelis-Menten kinetics and have calculated constants from Lineweaver-Burk reciprocal plots and Eadie-Hofstee plots. Another approach was therefore required to overcome the limitations and assumptions made in these studies. My first aim was therefore to determine the kinetics of L-arginine uptake into endothelial cells using a general non-linear approach, which allows initial rates of uptake by more than one transporter to be determined and importantly includes the actual concentrations of both the trace radiolabelled and unlabelled amino acid in the model. Furthermore, using this approach no assumptions are made regarding the type of inhibition and the concentrations of inhibitors (or activators) could be included in the model. As the model was additive, the theoretical contribution of uptake by each transporter could be modelled. The present study used raw, rather than transformed data, in non-linear regression analysis to characterize the kinetics of L-arginine uptake into cells. I modelled the initial high affinity/low capacity and low affinity/high capacity uptake of trace L-[3H]arginine by two transporters into ECV304 and umbilical cord vein endothelial cells in the presence of a range of unlabelled L-arginine and modifiers using GraphPad Prism. The contribution of uptake by individual transporters was modelled and showed that leucine inhibited the individual transporters differently and that the inhibition was not necessarily competitive. N-ethylmaleimide inhibited only y+ transport and 2-amino-bicyclo-[2,2,1]-heptane-2-carboxylic acid may be a potential inhibitor of y+L transport. Only the absence of sodium reduced L-arginine uptake by y+L transport and reduced the Km’, whereas reducing sodium decreased L-arginine uptake by y+ transport without affecting the Km’. This non-linear modelling approach allows more than one transporter to be modelled, overcomes many of the assumptions made in reported studies and by using raw, rather than transformed data, avoids the errors inherent in methods deriving constants from the linearization of the uptake processes following Michaelian kinetics. The results of this study therefore provide explanations for discrepancies in the literature and suggest that this modelling approach better characterises the kinetics of amino acid uptake into cells. Having elucidated the kinetics of L-arginine uptake into endothelial cells, I was then equipped to explore possible factors which could impair L-arginine uptake in hypertension. In this regard, although increases in total plasma homocysteine were thought to play a role in hypertension; large prospective clinical trials to reduce total plasma homocysteine by vitaminB6/12/folate supplementation, have failed to show beneficial effects on vascular outcomes. The effects of homocysteine on the vasculature were attributed to the reactive free sulphydryl group; however only a fraction (1.5 – 4%) of total plasma homocysteine is actually present as the free reduced sulphydryl (-SH or thiol) form. In comparison, free oxidized homocysteine, present as the disulphide, homocystine and the mixed disulphide (with cysteine) accounts for 20 – 30% of total plasma homocysteine. In the absence of a clear mechanism by which homocysteine causes vascular disease, one of the other species making up the total homocysteine may be contributing to vascular disease through a different mechanism which may not involve the free sulphydryl group. Earlier studies demonstrated (in isolated nephrons) that the homocysteine disulphide, homocystine, shared the same membrane transporter as L-arginine (the precursor of NO), and competed for uptake with L-arginine. These studies may suggest that increased homocystine concentrations, by inhibiting L-arginine transport, and hence reducing intracellular L-arginine concentrations, may impact on NO production in other cell types. Therefore, the second aim of my study was to determine the effects of homocystine on cellular L-arginine uptake and hence on NO production. The uptake of labelled L-[3H]arginine was measured in confluent, L-arginine depleted HUVEC and ECV304 cells with unlabelled L-arginine, without or with homocystine and modifiers. The kinetic constants were determined in Graphpad Prism using a described non-linear model of uptake for two transporters acting simultaneously. The NO specific fluorescent DAF-2 dye was used to detect NO production by the cells. Elevated physiological concentrations of 2.5μM homocystine significantly inhibited L-arginine uptake by 90% by y+L transport in both HUVEC (p<0.0005) and in ECV304 cells (p<0.05). Homocystine reduced the Kma of y+L transport in HUVEC (<0.0001) affecting uptake in a competitive-like manner. Pre-incubation of the ECV304 cells with L-arginine was able to reverse this inhibition by homocystine. In contrast, homocystine increased uptake by y+ transport in HUVEC (p<0.01). Under the experimental conditions used, effects of homocystine on the rate of NO production could not be shown. By demonstrating that homocystine nearly abolishes L-arginine uptake by y+L transport in both HUVEC and ECV304 cells, these data provide a mechanism as to how homocystine may affect L-arginine concentrations. These data would support studies to determine the association between homocystine concentrations and cardiovascular disease. Lastly, although angiotensin-converting enzyme inhibitors (ACEI’s, as well as angiotensin II receptor antagonists) but not other classes of antihypertensive agents, have been shown to decrease oxidative stress and increase NO availability independent of blood pressure lowering effects, the mechanism is not clear. The ability of ACEI’s to decrease oxidative stress and enhance NO production has been attributed in part to the sulfhydryl groups present in some, but not all, ACEI’s. Hence the mechanisms of the effects of ACEI’s on NO production warrant further investigation, as it is possible that L-arginine transporters may play a role by enhancing L-arginine uptake into cells, and thereby increasing NO production.

Thesis (Ph. D.)--University of Washington, 1996. / Vita. Includes bibliographical references (p. [104]-108).

Aneurysms occur throughout the length of the aorta, with a large proportion occurring in the infra-renal segment of the abdominal aorta (least 9 to 10 times more common than thoracic aortic aneurysms). Aneurysmal disease of the aorto-iliac segment which commonly occurs as a result of a degenerative process is invariably a progressive entity. Concomitant iliac artery aneurysms have been noted to occur in 15-40% of patients with abdominal aortic aneurysms (AAAs). As a result, following open AAA repair, there is a concern regarding the progressive enlargement of the iliac arteries. The aim of this study was to investigate the long term outcome of proximally excluded common iliac arteries (CIAs) following open bifurcated abdominal aortic aneurysm (AAA) repair. Baseline clinical and demographic data of 165 consecutive patients undergoing open AAA repair between April 2004 and April 2014 was collected. The aorta and iliac segments were measured in the 120 available preoperative Computed Tomographic (CT) angiograms. A single postoperative CT scan was performed and measurements recorded in 46 patients available for follow-up. The patients were grouped according to the type of surgical repair, open tube graft repair or bifurcated graft repair to the common iliac (CIA), external iliac artery (EIA) or common femoral artery (CFA). Entered into the study were 165 patients (133 men, 32 women) with a mean age of 66 years and a mean AAA diameter of 6.7cm (range 5.1 - 10.3cm). After a median follow-up of 49 months, 46 patients (88 CIAs) were available for a single postoperative CT scan.

Background: Peripheral arterial disease (PAD) is an established occlusive disease of the peripheral arteries and is not uncommon in the elderly. Atherosclerosis accounts for 90% of the pathology. Only 15% of affected individuals become symptomatic. Most symptomatic individuals present with intermittent claudication (IC). Only a small proportion (1%) of affected individuals present with critical limb ischaemia (CLI). Revascularization aimed at limb salvage, and recovery of ambulation and independent living is the ultimate therapeutic option for the advanced form of PAD (CLI). Traditionally, the success of revascularization for CLI has been defined by graft patency rates and limb salvage rates. Functional outcomes such as ischaemic wound healing and recovery of ambulatory function for independent living have been the focus in more recent publications. However, these assessments do not consider the patients' pre-operative metabolic profile as a predictor of postoperative outcomes. Purpose: The purpose of this study was to determine, in a prospective manner, the influence of preoperative metabolic profile on post-operative outcomes in contemporary patients with peripheral arterial disease presenting with critical limb ischaemia at a tertiary hospital in South Africa. Methods: All consecutive patients, ≥ 18 years, with CLI admitted to the vascular unit at Groote Schuur Hospital over a two-year period (1st January, 2015 to 31st December, 2016) with reconstructable disease were recruited for the study. Written informed consent was obtained from all participants. Revascularization entailed either open surgical revascularization, endovascular interventions or both (hybrid procedures). Data was analyzed according to the clinical level of disease and the type of surgical intervention. Post-operative outcome measures were determined. Primary endpoints (functional and technical outcomes) • Ambulatory recovery at six months and one year • Complete ischaemic wound healing at six months and one year • Limb salvage rate at six months and one year • Primary graft patency rate at six months and one year Secondary endpoint • The influence of pre-operative metabolic profile on the post-operative outcomes The association between pre-operative metabolic profile and post-operative outcomes was determined by Pearson Chi-square statistical test and logistic regression model. Results: A total of 73 consecutive patients were recruited for this study with a mean age of 58 ± 9 years (Range: 30 - 75 years). Seventeen patients (23.3%) had rest pain and 56 (76.7%) had tissue loss [Minor tissue loss was 47 (64.4%) and major tissue loss was 9 (12.3%)]. Current smokers and previous smokers constituted 86% of the sample population with a male to female ratio of approximately 1:1. Our study population was generally overweight based on the BMI. There was high prevalence of abdominal obesity and high body fat for both males and females. Recovery of ambulatory status was 69% and 67% at six months and one year follow-up respectively. The rate of ischaemic wound healing at six months and one year was 48.2% and 75.0% respectively. Surgical site sepsis was the most common local wound complication. Limb salvage rate was 78% and 79% at six months and one year respectively. Overall primary graft patency at six months was 69.0% but reduced to 60.0% at one year. Major amputation rate at one year was 21%. Most of the postoperative wound-related complications occurred among patients with diabetes. More diabetic patients had major amputations compared to non-diabetic patients (57.9% vs 42.1%). One year amputation-free survival (AFS) was 69.9%. There were no statistically significant associations between metabolic profile of patients and post-operative clinical outcomes. Conclusion: Demographics, co-morbidities, and procedural details of our study population, reflected a relatively younger population with CLI. The profile of this contemporary vascular surgery patients is that of overweight, high abdominal obesity, and high prevalence of smoking among both gender. The technical and functional outcomes observed in this study are consistent with available western literature. Diabetes was associated with prolonged ischaemic wound healing, higher risk of major amputation and local wound complications. A statistically significant association was not found between patients' metabolic profile and post-operative outcome but this could be due to the small sample size and short follow up period.

Background: Disturbances in metabolic homeostasis, resulting in cardiovascular disease, are the major cause of morbidity and mortality in patients with chronic kidney disease (CKD). Mineral deposition in the vascular smooth muscle cell (VSMC)-rich medial layer of the vessel wall is a prominent driver of mortality in these patients. Vascular calcification (VC) is now recognized as an important predictor and independent risk factor for all-cause and cardiovascular mortality in patients with advanced CKD. Prolonged impairment in kidney functions, characteristic of chronic CKD, results in marked changes in blood biochemistry, namely elevated circulating levels of inorganic phosphate (Pi) and calcium. These changes in circulating mineral content trigger osteogenic transdifferentiation and apoptosis of the VSMCs, subsequently leading to VC. In addition to kidney-related metabolic changes, chronic inflammation and liver disease are also associated with increased VC. T-cell death-associated gene 51 (TDAG51) and growth differentiation factor 10 (GDF10) have been previously reported to contribute to metabolic regulation in conditions of atherogenic VC, osteogenesis, and adipogenesis. However their role in medial VC and associated morbidities remains unknown. Methods and Results: Using a combination of in vitro, ex vivo and in vivo models findings presented in this thesis demonstrate that TDAG51 is an important modulator of VC, and as such is upregulated by conditions of hyperphosphatemia. I show that VSMCs from TDAG51-/- mice exhibit reduced expression and activity of key driver of osteogenic transdifferentiation, Runt-related transcription factor 2 (Runx2). To explain these observations, I demonstrate reduced expression of type III sodium-dependent Pi transporter, Pit-1, as well as intracellular Pi in these cells. Additionally, GDF10, an established inhibitor of osteogenesis, was identified to be significantly upregulated in TDAG51-/- VSMCs and mice. In line with these observations, knockdown of human homologue of TDAG51, pleckstrin homology-like domain, family A, member 1, resulted in increased expression of GDF10. Consistent with the anti-osteogenic role of GDF10, treatment with recombinant human GDF10 reduced Pi-mediated hydroxyapatite deposition, Runx2 expression and activity in primary mouse VSMCs. Interestingly, GDF10-/- mice develop severe adiposity, hepatic lipid accumulation, injury and inflammation. To explain this phenotype, a marked increase in the expression and activity of established driver of adipogenesis, peroxisome-proliferator-activated receptor γ (PPAR γ) in the livers of GDF10-/- mice was demonstrated. Complementary experiments in cultured hepatocytes demonstrate that treatment with recombinant human GDF10 attenuates nuclear PPAR γ expression and subsequent lipid accumulation, inflammation and fibrosis in these cells. Conclusion: This work highlights TDAG51 as an important regulator of Pi-mediated VC through downregulation of Pit-1, Runx2, and GDF10. Additionally, GDF10 has been described as a novel systemic inhibitor and a potential diagnostic marker for VC. Lastly, this work further characterizes GDF10 as an adipokine important in the regulation of hepatic lipid levels, which can indirectly affect vascular health. / Thesis / Doctor of Philosophy (Medical Science)

No description available.

痴呆是导致中风后存活人群自理能力降低的重要因素。中风后痴呆（PSD）包括发生在中风后的所有类型的痴呆，不论其痴呆的原因为何，如血管性痴呆(VD)，阿尔茨海默氏症(AD)以及混合型痴呆。由于中风致死率的降低和人口老龄化的到来，有可能在未来几十年，全世界范围内中风后痴呆的发病率将大幅增加。在此，我们将报告中风后早期出现的痴呆及长期的认知功能下降的发病率和危险因素，并通过使用PIB正电子扫描确定中风后痴呆中合并脑部淀粉样变的发病率。了解中风后痴呆的发病机制和危险因素，将有利于我们寻求治疗和预防措施，从而减低中风后痴呆的发生。 / 研究目的 / 研究1：中风后早期痴呆的发病率及危险因素 / 早期PSD及长期认知功能下降的发病机制甚为复杂。我们在中国中风存活者中建立了名为 STroke Registry IVEstigating COGnitive decline (STRIVE-COG) 的研究。此研究将报告早期PSD的危险因素。 / 研究2：中风后长期（15-18个月）认知功能下降的发病率及预测因素中风会增加远期痴呆的发生。但是，中风后远期认知功能下降的发病机制还未确定。我们的研究旨在观察中风后远期认知功能下降的危险因素。 / 研究方法 / 研究1：我们连续纳入一年的在我院中风中心留院的中风及短暂性缺血发作病人。在病人中风发生后的3-6个月后，对其进行多个认知领域的神经心理学检查。我们观察了患者的临床特征及结构影像学改变与早期PSD的相关性。我们还对部分早期PSD的病人进行了PIB正电子发射扫描（PIB-PET）检查。 / 研究2：在完成中风后3-6个月认知检查后的1年，即中风后的15-18个月，我们完成了认知心理学的随访检查。我们将认知功能下降定义为简易精神状态评分降低3分及以上，或者临床痴呆评分增加1分及以上。我们观察了认知功能下降和基线期临床、认知心理学和影像学特征（包括白质病变严重程度、陈旧性腔梗、全脑萎缩、额叶萎缩、顶叶萎缩、中颞叶萎缩）。在一组（n=18）早期PSD患者中，我们观察了脑部有类似阿尔茨海默氏病变表现的患者的认知功能下降的发病率。 / 结果 / 研究1：在所有入组的患者中（n=549），早期PSD的发病率为15.3%（n=84）。多因素回归分析显示，除了年龄和性别，早期PSD的危险因素包括急性腔隙性梗死灶(危险比[OR] 2.725, 95% 可信区间[CI] 1.364-5.434, P=0.004)及急性非腔隙性梗死灶(OR 2.809, 95%CI 1.124-6.410, P=0.014)比上无急性梗死灶的病人，还包括白质病变严重度（OR 1.120, 95% CI 1.037-1.210, p=0.004），额叶萎缩（OR 2.596, 95% CI 1.080-6.241, p=0.033），由脑室-大脑比表示的全脑萎缩（4th 四分卫区间 vs 1st区间, OR 3.096, 95% CI 1.374-6.993, p=0.006）。在19个完成了PIB-PET扫描的病人中，6人（31.6%）具有类似AD的脑部淀粉样物聚集的表现。 / 研究2：在452（82.3%）个完成了中风后15-18个月随访检查的病人中，认知功能下降的患者有73个（16.2%）。而年龄、受教育年限、多发陈旧性腔隙性梗死是其独立性预测因素。随访过程中中风复发的患者只有5.1%并且与认知功能下降无相关性。进展性的认知功能下降在PIB阴性（n=12）和PIB阳性（n=6）的患者中分别为41.7%和33.3%，而两者之间显著差别（p=0.731）。 / 结论 / 研究 1: 早期PSD的危险因素除了包括年龄、性别及脑部急性梗死灶之外，还包括脑部的慢性改变，包括白质病变、全脑萎缩、额叶萎缩及合并AD样病变特征。 / 研究 2: 年龄、受教育水平和多发陈旧性腔隙梗死是中风后15-18个月认知功能下降的独立危险因素。而合并AD样病变并不是导致中风后远期认知功能下降的必要因素。 / Dementia is a main cause of dependency in stroke survivors. Poststroke dementia (PSD) includes any dementia after a stroke, irrespective of its causes, e.g. vascular dementia (VD), Alzheimer’s disease (AD) or mixed dementia. A huge increase in prevalence and burden of PSD is likely to happen because of the decline in mortality after stroke and ageing of populations in the coming decades worldwide. In this thesis, we reported the risk factors for early PSD and delayed poststroke cognitive decline, and the prevalence of concurrent amyloid pathology as identified by Pittsburgh compound B (PIB) positron emission tomography (PET) in PSD. Understanding the risk factors of PSD will help to devise preventive and treatment strategies that may reduce the burden of PSD. / Objectives / Study1: Risk factors of early PSD / Mechanisms explaining poststroke early and delayed cognitive decline are complex. We set up a STroke Registry IVEstigating COGnitive decline (STRIVE-COG) among Chinese stroke survivors. Study 1 reported the findings on risk factors for early PSD. / Study 2: Prevalence and predictors for delayed (15-18 months) cognitive decline after stroke / Having a stroke increases the risk of delayed dementia. However, mechanisms accounting for the cognitive decline are uncertain. We investigated the predictors for delayed poststroke cognitive decline. / Subjects and Methods / Study 1：We recruited consecutive stroke or transient ischemic attack (TIA) patients admitted to our acute stroke unit over 1 year. We performed neuropsychological assessment 3-6 months poststroke. We investigated the association between clinical and structural neuroimaging features with early PSD. We performed PIB positron PET among a subset of subjects with early PSD. / Study 2: We performed neuropsychological assessment at baseline (i.e. 3-6 months poststroke) and at 15-18 months poststroke. We defined cognitive decline as a drop of ≥ 3 points in the mini-mental state examination and/or increment in ≥ 1 grading of the clinical dementia rating scale. We investigated the association between cognitive decline with baseline clinical, neuropsychological, and neuroimaging features (white matter changes [WMC] severity, old lacunar infarct, global atrophy, frontal lobe atrophy [FLA], parietal lobe atrophy, medial temporal lobe atrophy). Among a subset of subjects (n=18) with PSD at baseline, we investigated the influence of AD-like PIB retention upon the rate of cognitive decline. / Results / Study 1: Prevalence of early PSD among all recruited subjects (n=549) was 15.3% (n=84). Apart from age and female gender, multivariate regression analyses showed that risk factors for early PSD were presence of acute lacunar (odds ratio [OR] 2.725, 95% confidence interval [CI] 1.364-5.434, P=0.004) or non-lacunar infarct (OR 2.809, 95%CI 1.124-6.410,P=0.014) over no acute infarct apparent on neuroimaging, WMC severity (OR 1.120, 95% CI 1.037-1.210, p=0.004), FLA (OR 2.596, 95% CI 1.080-6.241, p=0.033), and global brain atrophy (4th quartile vs 1st quartile, OR 3.096, 95% CI 1.374-6.993, p=0.006). Among 19 subjects with early PSD who had PIB PET, 6 (31.6%) had AD-like PIB retention. / Study 2: Among 452(82.3%) subjects who had completed the study, cognitive decline occurred in 73 (16.2%) subjects. Age, education, and multiple old lacunar infarcts independenty predicted cognitive decline. Recurrent stroke occurred only in 5.1% and was not associated with cognitive decline. Progressive cognitive decline occurred in 41.7% and 33.3% of PIB negative (n=12) and PIB positive (n=6) PSD patients, respectively (p=0.731). / Conclusion / Study 1: Apart from age, female gender, and presence of acute infarct evident in neuroimaging, chronic brain changes (WMC, global brain atrophy, FLA, and concurrent AD pathology) are associated with early PSD. / Study 2: Age, education, and multiple old lacunar infarcts predicted cognitive decline at 15-18 months poststroke. Concurrent AD-like lesion is not necessary associated with a rapid cognitive decline. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Yang, Jie. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 93-109). / Abstract also in Chinese. / Chapter PART I --- LITERATURE REVIEW --- p.1 / Chapter Chapter 1 --- Introduction --- p.2 / Chapter 1.1 --- An overview of stroke --- p.2 / Chapter 1.2 --- Introduction of poststroke dementia --- p.5 / Chapter Chapter 2 --- Poststroke Dementia --- p.6 / Chapter 2.1 --- Defining poststroke dementia --- p.6 / Chapter 2.2 --- Classification of poststroke dementia --- p.7 / Chapter 2.3 --- Frequency, incidence, and clinical determinants of poststroke dementia --- p.20 / Chapter 2.4 --- Imaging methods and imaging features in poststroke dementia --- p.22 / Chapter 2.5 --- Mechanisms of stroke-associated dementia --- p.24 / Chapter 2.6 --- Influence of poststroke dementia on stroke outcome --- p.28 / Chapter PART II --- STUDIES ON EARLY POSTSTROKE DEMENTIA AND DELAYED COGNITIVE DECLINE --- p.31 / Chapter Chapter 3: --- Stroke Registry Investigating Cognitive decline (STRIVE-COG): Risk Factors for Early Poststroke Dementia (Study 1) --- p.32 / Chapter 3.1 --- Abstract --- p.32 / Chapter 3.2 --- Introduction --- p.33 / Chapter 3.3 --- Methods --- p.35 / Chapter 3.4 --- Results --- p.45 / Chapter 3.5 --- Discussion --- p.48 / Chapter Chapter 4 --- Stroke Registry Investigating Cognitive decline (STRIVE-COG): Predictors for Delayed Poststroke Cognitive decline (Study 2) --- p.63 / Chapter 4.1 --- Abstract --- p.63 / Chapter 4.2 --- Introduction --- p.64 / Chapter 4.3 --- Methods --- p.66 / Chapter 4.4 --- Results --- p.76 / Chapter 4.5 --- Discussion --- p.78 / Chapter PART III --- CONCLUSION --- p.88 / Chapter Chapter 5 --- Strengths and Limitations --- p.89 / Chapter Chapter 6 --- Summary and Future Directions --- p.91 / References --- p.93

Muscular dystrophy is a disease characterized by skeletal muscle weakness and wasting, but little is known of alterations in the vascular system that occur with this disease. The culprit in many muscular dystrophies is a defective dystrophin-glycoprotein complex (DGC). The DGC is a group of transmembrane proteins that connects the cytoskeleton of muscle cells to the extracellular matrix; it plays a role in mechanotransduction and the maintenance of structural integrity of these cells, and includes the proteins dystrophin and sarcoglycan-delta. The absence of these proteins results in severe muscular dystrophies in humans, and thus knockout mice lacking the genes encoding for dystrophin (mdx mice) and sarcoglycan-delta (sgcd-/- mice) were studied to detect any vascular alterations that occur as a result of a defective DGC. Acute biaxial biomechanical data were obtained through pressure-diameter and axial force-length tests on common carotid arteries of mdx, sgcd-/-, and wild-type mice in the active and passive smooth muscle state. Functional response to the vasoreactive compounds phenylephrine, carbamylcholine chloride, and sodium nitroprusside was also tested. We found significant biomechanical differences between the knockout and wild-type mouse arteries: the mdx and sgcd-/- arteries had decreased distensibilities in pressure-diameter tests, with mdx arteries also having increased circumferential stresses, and the knockout arteries generated increased axial loads and stresses in the axial force-length tests. The mdx and sgcd-/- arteries also differed from the wild-type in that their ‘homeostatic’ axial stretch, at which the axial force remains constant upon pressurization, was significantly decreased. We conclude that the loss of DGC proteins does trigger changes in vascular smooth muscle cells or their interactions with the extracellular matrix, yet that the altered vascular system was able to adapt and function without the DGC. Knowledge of alterations to the vascular system (and adaptations to these changes) of patients with muscular dystrophy could help physicians customize their treatment to extend and enhance their lives, especially as medical advances extend the lifespan of these patients and they begin to suffer from diseases such as hypertension and atherosclerosis that affect the normal aging population.