Jun Zhang1, Teodoro Bottiglieri2, Peter A McCullough1,3,4,5. 1. Baylor Heart and Vascular Institute, TX, USA. 2. Institute of Metabolic Disease, Baylor Research Institute, TX, USA. 3. Department of Internal Medicine, Baylor University Medical Center, TX, USA. 4. Baylor Jack and Jane Hamilton Heart and Vascular Hospital, Dallas, TX, TX, USA. 5. The Heart Hospital Baylor Plano, Plano, TX, USA.
Abstract
BACKGROUND: Endothelial dysfunction (ED) has emerged as a critical process in cardiorenal syndrome (CRS). The concept that ED is closely linked with cardiac and renal dysfunction has become an important target for CRS-related research and clinical practice. SUMMARY: The sequence of events leading to ED is initiated by type I endothelial activation (almost immediately) and type II endothelial activation (over hours, days, and even months), followed by endothelial apoptosis and endothelial necrosis. The fact that ED is a continual cellular event divides this process into reversible ED (endothelial activation) and irreversible ED (endothelial apoptosis and necrosis). This basic research-defined concept may have clinical implications. Although most antihypertensive drugs (ACE inhibitors, statins, etc.) are effective in patients with hypertension and diabetes, some of them have proved to be ineffective, which may partly be attributed to irreversible ED. Even though the etiology of ED consists mainly of asymmetric dimethylarginine, nitric oxide, oxidative stress, and anti-endothelial cell antibodies, many other inducers of ED have been identified. In addition, a distinct role of ED has been reported for each type of CRS in humans. KEY MESSAGES: Further study is warranted to prove whether ED holds promise as a pharmacological target in CRS patients.
BACKGROUND: Endothelial dysfunction (ED) has emerged as a critical process in cardiorenal syndrome (CRS). The concept that ED is closely linked with cardiac and renal dysfunction has become an important target for CRS-related research and clinical practice. SUMMARY: The sequence of events leading to ED is initiated by type I endothelial activation (almost immediately) and type II endothelial activation (over hours, days, and even months), followed by endothelial apoptosis and endothelial necrosis. The fact that ED is a continual cellular event divides this process into reversible ED (endothelial activation) and irreversible ED (endothelial apoptosis and necrosis). This basic research-defined concept may have clinical implications. Although most antihypertensive drugs (ACE inhibitors, statins, etc.) are effective in patients with hypertension and diabetes, some of them have proved to be ineffective, which may partly be attributed to irreversible ED. Even though the etiology of ED consists mainly of asymmetric dimethylarginine, nitric oxide, oxidative stress, and anti-endothelial cell antibodies, many other inducers of ED have been identified. In addition, a distinct role of ED has been reported for each type of CRS in humans. KEY MESSAGES: Further study is warranted to prove whether ED holds promise as a pharmacological target in CRS patients.
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