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Traditional indicators of cardiovascular disease (CVD) risk may not be appropriate for Asian Indians. We designed a cross-sectional study of body fat distribution, apoB/apoA1 ratio and adipokines of Northern Indians compared to Caucasians to determine if there is a different relationship between these parameters. Indian (men: n = 54; women n = 28) and Caucasian (men: n= 32; women, n = 51) subjects were recruited who were between the ages of 20 and 60 years. Subjects were excluded if they had a history of CVD or were taking lipid lowering medications. Body fat percentage (BF%) was measured using bioelectrical impedance analysis. Indian subjects had a substantially higher waist-to-hip ratio (WHR) ratio than Caucasian subjects (men: 0.93 +/- 0.01 vs. 0.86 +/- 0.01, p < 0.001; women: 0.88 +/- 0.01 vs. 0.76 +/- 0.01, p < 0.0001). Interestingly, while WHR correlated strongly with BF% in Caucasians (men: r = 0.63 p = 0.0002; women: r = 0.74, p < 0.0001, respectively) there was no correlation in Indians (men: r = 0.22, ns; women: r = 0.23, ns). The regression lines for WHR vs. BF% of Indians compared to Caucasians was significantly different (men p = 0.02, women p = 0.002). A similar pattern of correlation was seen with WHR and BMI. In addition, Indian men and women had a higher apoB/A1 ratio than Caucasians: the most powerful lipoprotein measure of CVD risk (men: 0.84+/-0.04 vs. 0.66+/-0.04, p=0.001; women: 0.70+/-0.04 vs. 0.56+/-0.03, p = 0.003, respectively). Leptin levels were higher and adiponectin levels in lower in the Indian men and women. Hypothetically, these alterations in body composition, apoB/apoA1 and adipokines could be due to alterations in adipocyte number.

Hyperhomocysteinemia is a risk factor for cardiovascular disease and stroke. Nutritional and/or genetic disruptions in homocysteine metabolism can cause hyperhomocysteinemia. Mild methylenetetrahydrofolate reductase (MTHFR) deficiency due to the 677C → T mutation in the MTHFR gene is the most common genetic cause of hyperhomocysteinemia. The 677C → T variant is associated with an increased risk for neural tube defects, pregnancy complications, schizophrenia and Down syndrome, and with a decreased risk for colon cancer and leukemia. This variant is also a potential risk factor for vascular disease. Severe MTHFR deficiency results in homocystinuria, an inborn error of metabolism with neurological and vascular complications. We have generated mice with a knockout of the Mthfr gene. The Mthfr-deficient mice exhibit hyperhomocysteinemia and decreased methylation capacity. The Mthfr+/- mice appear normal, whereas the Mthfr-/- mice are smaller and have reduced survival. Abnormal external granule neuron development associated with increased cell death in the cerebellum was observed in the Mthfr-/- mice. / Evidence for cardiovascular pathology was obtained in several ways. Impaired aortic relaxation response to acetylcholine was seen in the Mthfr +/- mice fed a high methionine diet. Both Mthfr+/- and Mthfr-/- mice fed a low folate high methionine diet developed myocardial fibrosis in the left ventricle. Abnormal lipid deposition in the proximal portion of the aorta was observed in older Mthfr+/- and Mthfr-/- mice. After crossing Mthfr -deficient mice with apoE-null mice, we demonstrated that MTHFR deficiency promoted atherogenesis and its progression in the apoE-null mice. / Gene expression in brain of Mthfr-deficient mice was investigated via microarray analysis. Five genes with altered expression in the brain of Mthfr-/- mouse were validated by RT-PCR. In biochemical studies of human MTHFR, both FAD and folate were shown to stabilize the purified recombinant wild type and mutant MTHFRs from the baculovirus expression system against heat inactivation. The effect of folate appeared to be secondary to that of FAD, and S-adenosylmethionine (SAM) inhibited purified wild type and mutant MTHFRs with similar efficiency. / This dissertation will significantly contribute to our understanding of the role of MTHFR in human disease.

Access to abstract permanently restricted to Ball State community only / Access to thesis permanently restricted to Ball State community only / School of Physical Education, Sport, and Exercise Science

Access to abstract permanently restricted to Ball State community only / Access to thesis permanently restricted to Ball State community only / School of Physical Education, Sport, and Exercise Science

Access to abstract permanently restricted to Ball State community only / Access to thesis permanently restricted to Ball State community only / Department of Physiology and Health Science

Purpose: Cardiac rehabilitation (CR) programs have been shown to promote numerous health benefits among patients with cardiovascular disease (CVD), but little is known about the characteristics of CR programs. Methods: A survey was developed and utilized to collect data on Early Outpatient Cardiac Rehabilitation programs (EOCR) in the USA. An email with a link to the survey was sent by the American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR) to their members. Program directors/administrators were recruited to provide information about their program in operation during 2009 in the United States. The CR survey contained 13 questions, some with multiple answers, regarding the utilization and patient demographics of an Early Outpatient Cardiac Rehabilitation (Phase II) program. Results: Responses were received from 138 programs in 44 states. Of the responses, 19,689 patients completed at least one EOCR exercise session. Of the responses, 68% of patients were men and 32% of patients were women. Patients enrolled in EOCR programs had a primary diagnosis of CABG 4,803 (30%); AVR/MVR 1,401(9%); MI 3,583 (22%); PCI/Stent 4,961 (31%); stable angina 965 (6%); heart/lung transplant 53 (0.33%); other 385 (2%). 8.4% complete 0-6 sessions of EOCR; 12% complete 7-12 sessions; 22% complete 13-18 sessions; and 58% complete 19-36 sessions. 35% of patients enrolled in EOCR programs are discharged early. 84% of programs offer an outpatient maintenance CR program. 96% of EOCR programs offer education classes; 89% offer resistance equipment; 72% are AACVPR certified; 62% also offer pulmonary rehabilitation; 23% utilize outcome measurements; 62% are in rural locations; and the average patient-to-staff ratio is 4.2:1. Conclusions: CR programs are used by a minority of eligible patients. There is marked variation in the structure and content of EOCR programs. Alternative strategies to improve standardization and outcomes should be implemented. / School of Physical Education, Sport, and Exercise Science

Autoantibodies generated against M proteins can cause post-streptococcal disorders such as Rheumatic Fever. A severe complication of rheumatic fever is rheumatic heart disease which may involve both cardiomyopathy and valvulitis. Rheumatic fever has been associated with the class I M protein epitope of Group A streptococcus (GAS). This epitope can be recognized by monoclonal antibodies (mAbs) 10B6 and 10F5. Previously, we demonstrated binding of streptococcal mAb10F5 in the heart tissue (apex, atria, and valves) of Lewis rats as compared to anti-myosin binding. To determine if mAb10F5 binding in the heart is due to virulence of the antibody or antibody subtype, rats were injected with control IgG2 antibodies and euthanized after 24, 48, or 72 hrs. Hearts were harvested and immunofluorescence was used to analyze the hearts. The immunofluorescence intensities for IgG2b were compared to mAb10F5 using previously acquired data. Control IgG2b rats showed significantly less immunofluorescence intensities in the heart regions than mAb10F5 injected rats at the 48 and 72 hr time points. These findings reaffirm mAb10F5 as an anti-cardiac antibody thatbinds heart tissue due its own virulence. To differentiate between the two IgG subtypes, binding intensities of IgG2a were compared to the binding intensities of IgG2b. The binding intensities of IgG2a increased with time. This finding was supported by previous work in our laboratory suggesting IgG2a remained in the bloodstream longer than the IgG2b. / Access to thesis permanently restricted to Ball State community only. / Department of Physiology and Health Science

Access to abstract permanently restricted to Ball State community only. / Access to thesis permanently restricted to Ball State community only. / School of Physical Education, Sport, and Exercise Science

Epidemiological studies have suggested that the consumption of fish may reduce the risk of cardiovascular disease. Compared to the number of studies using fish oils, few studies have used fish itself. Those which have used fish have generally used fattier fish such as mackerel and salmon as part of an uncontrolled diet. In this study, 23 healthy men consumed 200g each of Chinook salmon, Dover sole, and sablefish in a three-way crossover design for 18-day periods with three-week washout periods in between. The diets had the approximate composition of the 'Western' diet: 45% carbohydrates, 36% fat, and 16% protein with the sole diet containing 1.95 g omega-3 (n-3) fatty acids, the salmon diet 3.99 g n-3, and the sablefish diet 3.42 g n-3 fatty acids. Serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), bleeding time (BT), blood pressure (BP), platelet aggregation (PA) using ADP and collagen as agonists, platelet fatty acid profiles (FAP), thromboxane B2 (TXB2) , and apolipoprotein B (Apo B) were measured at the beginning and end of each period. TC, and HDL-C, and TG changed significantly when compared to the prefish diet while both LDL-C and apo B demonstrated diet effect. LDL-C increased on both the salmon and sablefish diets (p = 0.08) compared to the sole diet, and increased approximately 15% on the former two diets compared to the prefish diet. Bleeding time was significantly longer when the salmon diet was consumed (p = 0.06). The impact of the three diets on PA depended upon the agonist. With collagen, only the sablefish diet decreased aggregation compared to the prefish diet. When ADP was used, aggregation decreased on both the fattier fish diets compared to the low fat fish (sole). Similar results were demonstrated for TXB₂: the fattier fish produced statistically equivalent decreases (p = 0.06) among the diets, and lowered TXB₂ compared to the prefish diet. There were no significant differences among the diets for either systolic or diastolic BP though there was a significant decrease (p = 0.01) in diastolic pressure compared to the prefish diet when the salmon diet was consumed. Platelet fatty acid profiles reflected diet composition. / Graduation date: 1993