The Central Role of Endothelial Dysfunction in Cardiorenal Syndrome

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.

The Role of Dendritic and Endothelial Cells in Cardiorenal Syndrome

“…Our observations, in addition to data on endothelial dysfunction [14] and heart-kidney cross talk in the setting of immune system cells [7], suggest that professional antigen-presenting cells (DCs, monocytes, macrophages, B cells), nonprofessional antigen-presenting cells (ECs), and other immune cells (lymphocytes, neutrophils, etc.) play an important role in innate and adaptive immune responses to CRS.…”

“…By expressing MHC class I and II antigens, ECs also contribute to immune responses [69]. Like DC activation and maturation, EC activation and dysfunction play a pivotal role in the pathogenesis of CRS [14]. Regarding immune responses in CRS, it is unknown whether ECs may serve as antigen-presenting cells or act synergistically with DCs to actively participate in innate and adaptive immune responses.…”

“…Therefore, endothelial dysfunction has emerged as a critical process in CRS [14]. Recently, endothelial dysregulation has been reported to be associated with type 2 CRS, type 1 diabetes mellitus, and chronic CRS [15-17].…”

Statins and New-Onset Diabetes in Cardiovascular and Kidney Disease Cohorts: A Meta-Analysis

“…The benefits of preventing major adverse cardiovascular outcomes in patients with and without diabetes in comparison to the small, yet significant, risk of NODM is favorably balanced by the cardiovascular benefits [35-38]. This suggests that clinical decision-making should not change, especially for those with a medium or high risk of cardiovascular events or existing cardiovascular disease.…”

Mono- Or Combined Antihypertensive Therapy in Women With Arterial Hypertension and Moderate Risk of Cardiovascular Diseases: What’s Better?

“…В этих условиях происходит повы-шение концентрации АДМА, который реализует свой Комбинированная терапия Монотерапия провоспалительный и профиброгенный потенциал путем накопления коллагена в клубочках и афферент-ных артериолах, увеличивая экспрессию эндостатина, способного взаимодействовать с экспрессируемыми почечными эндотелиоцитами [17]. Наряду с этим, АДМА, накапливающийся в сыворотке крови больных АГ, по мере ухудшения функции почек усиливает свой эндоте-лийтоксический потенциал, вызывая разобщение e-NOS, подавление выработки оксида азота и повышение син-теза супероксида [18,19]. Как видно из полученных нами данных, в исходном состоянии у всех пациенток отмечалось повышение концентрации АДМА почти в 2 раза по сравнению с референсными значениями, что свидетельствует о раннем вовлечении в патологический процесс при АГ сосудистого эндотелия.…”