| dc.identifier.uri | http://hdl.handle.net/11401/76747 | |
| dc.description.sponsorship | This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. | en_US |
| dc.format | Monograph | |
| dc.format.medium | Electronic Resource | en_US |
| dc.language.iso | en_US | |
| dc.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dc.type | Dissertation | |
| dcterms.abstract | Cardiovascular disease is a major health concern for adults and youths in the United States. Over the past several decades many drug therapies have been designed to help combat this disease, however, the prevalence of risk factors (e.g., diabetes, obesity, hypercholesterolemia, and hypertension) is still high. According to the CDC, about 75 million American adults suffer from hypertension and 1,100 deaths each day are due to hypertension. Therefore, effectively controlling, and or preventing the occurrence of hypertension will lead to a further increase in life expectancy along with a better quality of life. To accomplish this, interventions that target specific genes associated with hypertension is imperative. The phospholipase D (PLD) enzyme superfamily is known for its role in signal transduction leading to endocytosis, intracellular vesicle trafficking, cell migration, and survival. Novel physiological activities for PLD have been reported, including the role of isoform PLD2 in the development of hypertension and atherosclerosis because of its interaction with angiotensin II type 1 receptor and its regulation of peroxisome proliferator-activated receptor-γ. In part, the work presented in this dissertation reveals a novel role for PLD2 in the development of hypertension through the endothelial nitric oxide synthase (eNOS) pathway. Using a PLD2-/- mouse model and shRNA gene silencing in endothelial cells, we show that PLD2-/- results in a decrease in eNOS abundance and subsequent nitric oxide (NO) production, ultimately causing a significant increase in mice systemic blood pressure. Finally, this dissertation also elucidates PLD2’s role in cholesterol internalization and the development of atherosclerosis. Using PLD2-/- mice and primary macrophage isolation, we that PLD2-/- mice may be more susceptible to arterial plaque deposition and development of atherosclerosis, due to a decrease in reverse cholesterol transport exhibited by a significant decrease in liver fatty accumulation and ATP-binding cassette transporter ABCA1 protein and mRNA levels. | |
| dcterms.abstract | Cardiovascular disease is a major health concern for adults and youths in the United States. Over the past several decades many drug therapies have been designed to help combat this disease, however, the prevalence of risk factors (e.g., diabetes, obesity, hypercholesterolemia, and hypertension) is still high. According to the CDC, about 75 million American adults suffer from hypertension and 1,100 deaths each day are due to hypertension. Therefore, effectively controlling, and or preventing the occurrence of hypertension will lead to a further increase in life expectancy along with a better quality of life. To accomplish this, interventions that target specific genes associated with hypertension is imperative. The phospholipase D (PLD) enzyme superfamily is known for its role in signal transduction leading to endocytosis, intracellular vesicle trafficking, cell migration, and survival. Novel physiological activities for PLD have been reported, including the role of isoform PLD2 in the development of hypertension and atherosclerosis because of its interaction with angiotensin II type 1 receptor and its regulation of peroxisome proliferator-activated receptor-γ. In part, the work presented in this dissertation reveals a novel role for PLD2 in the development of hypertension through the endothelial nitric oxide synthase (eNOS) pathway. Using a PLD2-/- mouse model and shRNA gene silencing in endothelial cells, we show that PLD2-/- results in a decrease in eNOS abundance and subsequent nitric oxide (NO) production, ultimately causing a significant increase in mice systemic blood pressure. Finally, this dissertation also elucidates PLD2’s role in cholesterol internalization and the development of atherosclerosis. Using PLD2-/- mice and primary macrophage isolation, we that PLD2-/- mice may be more susceptible to arterial plaque deposition and development of atherosclerosis, due to a decrease in reverse cholesterol transport exhibited by a significant decrease in liver fatty accumulation and ATP-binding cassette transporter ABCA1 protein and mRNA levels. | |
| dcterms.available | 2017-09-20T16:51:06Z | |
| dcterms.contributor | Lin, Richard | en_US |
| dcterms.contributor | Frohman, Michael | en_US |
| dcterms.contributor | El-Maghrabi, M. Raafat | en_US |
| dcterms.contributor | Girnun, Geoffrey. | en_US |
| dcterms.creator | Nelson, Rochelle Kisha | |
| dcterms.dateAccepted | 2017-09-20T16:51:06Z | |
| dcterms.dateSubmitted | 2017-09-20T16:51:06Z | |
| dcterms.description | Department of Physiology and Biophysics | en_US |
| dcterms.extent | 161 pg. | en_US |
| dcterms.format | Application/PDF | en_US |
| dcterms.format | Monograph | |
| dcterms.identifier | http://hdl.handle.net/11401/76747 | |
| dcterms.issued | 2017-05-01 | |
| dcterms.language | en_US | |
| dcterms.provenance | Made available in DSpace on 2017-09-20T16:51:06Z (GMT). No. of bitstreams: 1
Nelson_grad.sunysb_0771E_13314.pdf: 10775949 bytes, checksum: 1667a29cdf72ed17c456b8a1720e4f58 (MD5)
Previous issue date: 1 | en |
| dcterms.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dcterms.subject | Biology -- Cellular biology | |
| dcterms.subject | Atherosclerosis, eNOS, Hypertension, Phospholipase D2 | |
| dcterms.title | Effects of Phospholipase D2 on Cardiovascular Function and Disease | |
| dcterms.type | Dissertation | |
