Hyperoxia exposure in an aging model of type 1 diabetes

1 型糖尿病衰老模型中的高氧暴露

• 批准号: 10161682
• 负责人: Siva Kumar Panguluri
• 金额: $ 7.48万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-15 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10161682
• 关键词: Acute Lung Injury; Acute respiratory failure; Admission activity; Age; Aging; American; Animal Model; Arrhythmia; Biochemical; Cardiac; Cardiovascular Diseases; Cardiovascular system; Caring; Cells; Cerebrum; Cessation of life; Complication; Congestive Heart Failure; Coronary; Critical Care; Critical Illness; Data; Defect; Development; Diabetes Mellitus; Diagnosis; Disease; Echocardiography; Elderly; Electrocardiogram; Electrophysiology (science); Female; Functional disorder; Gender; Goals; Health Care Costs; Health Personnel; Heart; Heart Rate; Hospital Mortality; Hyperoxia; Hypoxia; Incidence; Insulin-Dependent Diabetes Mellitus; Investigation; Kidney; Kv channel-interacting protein 2; Left Ventricular Hypertrophy; Left ventricular structure; Life; Life Expectancy; Mechanics; Methods; Modeling; Molecular; Molecular Analysis; Mus; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Oxygen; Oxygen Therapy Care; Patch-Clamp Techniques; Patients; Physiological; Population; Predisposition; Publishing; Regulation; Reporting; Risk; Risk Factors; Sex Differences; System; Ventricular Remodeling; Wild Type Mouse; Woman; age related; aged; base; cardiovascular disorder risk; cardiovascular risk factor; comorbidity; constriction; coronary fibrosis; diabetic patient; differential expression; epidemiology study; experimental study; high risk; insight; male; men; mortality; mortality risk; non-diabetic; novel; older patient; patch clamp; prevent; pulmonary function; response; targeted treatment; ventilation

Project Summary: Patients in the ICU are routinely administered high levels of oxygen for the treatment of hypoxia in acute lung injury, congestive heart failure, cardiac fibrosis, and in other critical illness. However, high oxygen treatment (95%) also results in hyperoxia and subsequent constriction of the coronary, cerebral, and renal vasculatures. High mortality has been reported in patients with hyperoxia. Diabetes is one of the most common comorbid conditions in ICU patients, who undergo ventilation with high oxygen. The American Diabetes Association (ADA) estimates that there are approximately 1.25 million Americans currently living with type 1 diabetes (T1D). Cardiovascular disease (CVD) is a well-known complication of T1D and represents a major concern for patients and healthcare providers alike and are the leading cause of mortality in T1D. Men with T1D are at a 3.6-fold higher risk for CVD than nondiabetics, while women are at a 7.7-fold higher risk of CVD than nondiabetics. To date, there have been no studies that establish the cardiovascular risk of male and female T1D patients, who undergo hyperoxia exposure, in an aging study. In this study, we will investigate cardiac remodeling and electrical remodeling in hyperoxia-treated T1D male and female mice, using functional, molecular, and biochemical methods. Additionally, we will investigate hyperoxia exposures in both young and old T1D (Akita) mice. We will further determine physiological changes which occur in T1D young and old hearts, as a result of hyperoxia, using whole-cell patch-clamping technique. Our recent investigations suggest that regulation of Kv4.2, KChIP2 and Kv1.5 may be the major cause for pathophysiology of hyperoxia- induced hearts. Thus, we expect Kv channel dysregulation to underlie hyperoxia-induced electrical remodeling in T1D mouse hearts, including development of arrhythmias and defects repolarization. Overall, this proposal will help to further our current understanding of the physical, molecular and biochemical changes regarding ventricular remodeling and electrical remodeling in hyperoxia conditions in T1D. Thus, our proposal is crucial to clarify disease development and progression in hyperoxia exposure in T1D, but also to develop targeted therapy for T1D in critical care settings.

项目总结:

项目成果

The implications of hyperoxia, type 1 diabetes and sex on cardiovascular physiology in mice.

• DOI: 10.1038/s41598-021-02550-2
• 发表时间: 2021-11-29
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Bojkovic K;Rodgers JL;Vichare R;Nandi A;Mansour H;Saleem F;Abidin ZU;Vanthenapalli S;Cheng F;Panguluri SK
• 通讯作者: Panguluri SK

Influence of Age on Hyperoxia-Induced Cardiac Pathophysiology in Type 1 Diabetes Mellitus (T1DM) Mouse Model.

• DOI: 10.3390/cells12111457
• 发表时间: 2023-05-24
• 期刊: CELLS
• 影响因子: 6
• 作者: Saleem, Faizan;Mansour, Hussein;Vichare, Riddhi;Ayalasomayajula, Yashwant;Yassine, Jenna;Hesaraghatta, Anagha;Panguluri, Siva Kumar
• 通讯作者: Panguluri, Siva Kumar