Maternal N-acetylcysteine therapy regulates hydrogen sulfide-generating pathway and prevents programmed hypertension in male offspring exposed to prenatal dexamethasone and postnatal high-fat diet

2017

Toxins

197

195

Asymmetric and symmetric dimethylarginine (ADMA and SDMA, respectively) are toxic, non-proteinogenic amino acids formed by post-translational modification and are uremic toxins that inhibit nitric oxide (NO) production and play multifunctional roles in many human diseases. Both ADMA and SDMA have emerged as strong predictors of cardiovascular events and death in a range of illnesses. Major progress has been made in research on ADMA-lowering therapies in animal studies; however, further studies are required to fill the translational gap between animal models and clinical trials in order to treat human diseases related to elevated ADMA/SDMA levels. Here, we review the reported impacts of ADMA and SDMA on human health and disease, focusing on the synthesis and metabolism of ADMA and SDMA; the pathophysiological roles of these dimethylarginines; clinical conditions and animal models associated with elevated ADMA and SDMA levels; and potential therapies against ADMA and SDMA. There is currently no specific pharmacological therapy for lowering the levels and counteracting the deleterious effects of ADMA and SDMA. A better understanding of the mechanisms underlying the impact of ADMA and SDMA on a wide range of human diseases is essential to the development of specific therapies against diseases related to ADMA and SDMA.

Section: Potential Therapies For Reducing Adma and Sdma Levelsmentioning

confidence: 99%

Toxic Dimethylarginines: Asymmetric Dimethylarginine (ADMA) and Symmetric Dimethylarginine (SDMA)

2017

Toxins

197

195

“…It is highly vulnerable to oxidant injury. A number of animal models suggest oxidative stress involved in renal programming, including caloric restriction [40], maternal diabetes [41], prenatal dexamethasone exposure [43], high fructose intake [50], prenatal dexamethasone and postnatal high-fat diet [51], preeclampsia [52,53], maternal smoking [54], and low-protein diet [55]. Additionally, emerging evidence supports that NO-ROS imbalance is important for programmed hypertension [15,56].…”

Section: Mechanisms Of Renal Programmingmentioning

confidence: 99%

“…Glutathione (GSH) is the major intracellular antioxidant [112]. Our previous study demonstrated that N -acetylcysteine can increase GSH and reduce oxidative stress to prevent the development of hypertension in different models of renal programming [51,52,53]. Additional studies are required to unravel the impacts of the glutathione pathway on oxidative stress and programmed kidney disease.…”

Section: Changes In Renal Transcriptome In Response To Early-life mentioning

confidence: 99%

Developmental Origins of Chronic Kidney Disease: Should We Focus on Early Life?

2017

IJMS

Self Cite

103

Chronic kidney disease (CKD) is becoming a global burden, despite recent advances in management. CKD can begin in early life by so-called “developmental programming” or “developmental origins of health and disease” (DOHaD). Early-life insults cause structural and functional changes in the developing kidney, which is called renal programming. Epidemiological and experimental evidence supports the proposition that early-life adverse events lead to renal programming and make subjects vulnerable to developing CKD and its comorbidities in later life. In addition to low nephron endowment, several mechanisms have been proposed for renal programming. The DOHaD concept opens a new window to offset the programming process in early life to prevent the development of adult kidney disease, namely reprogramming. Here, we review the key themes on the developmental origins of CKD. We have particularly focused on the following areas: evidence from human studies support fetal programming of kidney disease; insight from animal models of renal programming; hypothetical mechanisms of renal programming; alterations of renal transcriptome in response to early-life insults; and the application of reprogramming interventions to prevent the programming of kidney disease.

“…Since cardiovascular phenotypes often develop after a prolonged asymptomatic phase in childhood and for the sake of brevity, we have restricted this review to data obtained from adult offspring. Here we summarize in Table 1 studies documenting cardiovascular programming related to oxidative stress [43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68]. …”

Section: Impact Of Oxidative Stress On Cardiovascular Programming mentioning

confidence: 99%

Interplay between Oxidative Stress and Nutrient Sensing Signaling in the Developmental Origins of Cardiovascular Disease

2017

IJMS

Self Cite

Cardiovascular disease (CVD) presents a global health burden, despite recent advances in management. CVD can originate from early life by so-called “developmental origins of health and disease” (DOHaD). Epidemiological and experimental evidence supports that early-life insults can induce programming of later CVD. Underlying the DOHaD concept, early intervention may offset programming process to prevent the development of CVD, namely reprogramming. Oxidative stress and nutrient sensing signals have been considered to be major mechanisms of cardiovascular programming, while the interplay between these two mechanisms have not been examined in detail. This review summarizes current evidence that supports the link between oxidative stress and nutrient sensing signaling to cardiovascular programming, with an emphasis on the l-arginine–asymmetric dimethylarginine (ADMA)–nitric oxide (NO) pathway. This review provides an overview of evidence from human studies supporting fetal programming of CVD, insight from animal models of cardiovascular programming and oxidative stress, impact of the l-arginine–ADMA–NO pathway in cardiovascular programming, the crosstalk between l-arginine metabolism and nutrient sensing signals, and application of reprogramming interventions to prevent the programming of CVD. A greater understanding of the mechanisms underlying cardiovascular programming is essential to developing early reprogramming interventions to combat the globally growing epidemic of CVD.