Insulin resistance is associated with subclinical vascular disease that is not justified by conventional cardiovascular risk factors,such as smoking or hypercholesterolemia.Vascular injury associated to insulin resist...Insulin resistance is associated with subclinical vascular disease that is not justified by conventional cardiovascular risk factors,such as smoking or hypercholesterolemia.Vascular injury associated to insulin resistance involves functional and structural damage to the arterial wall that includes impaired vasodilation in response to chemical mediators,reduced distensibility of the arterial wall(arterial stiffness),vascular calcification,and increased thickness of the arterial wall.Vascular dysfunction associated to insulin resistance is present in asymptomatic subjects and predisposes to cardiovascular diseases,such as heart failure,ischemic heart disease,stroke,and peripheral vascular disease.Structural and functional vascular disease associated to insulin resistance is highly predictive of cardiovascular morbidity and mortality.Its pathogenic mechanisms remain undefined.Prospective studies have demonstrated that animal protein consumption increases the risk of developing cardiovascular disease and predisposes to type 2 diabetes(T2D)whereas vegetable protein intake has the opposite effect.Vascular disease linked to insulin resistance begins to occur early in life.Children and adolescents with insulin resistance show an injured arterial system compared with youth free of insulin resistance,suggesting that insulin resistance plays a crucial role in the development of initial vascular damage.Prevention of the vascular dysfunction related to insulin resistance should begin early in life.Before the clinical onset of T2D,asymptomatic subjects endure a long period of time characterized by insulin resistance.Latent vascular dysfunction begins to develop during this phase,so that patients with T2D are at increased cardiovascular risk long before the diagnosis of the disease.展开更多
Cardiovascular disease poses the greatest risk of premature death seen among patients with chronic kidney disease(CKD).Up to 50% of mortality risk in the dialysis population is attributable to cardiovascular disease a...Cardiovascular disease poses the greatest risk of premature death seen among patients with chronic kidney disease(CKD).Up to 50% of mortality risk in the dialysis population is attributable to cardiovascular disease and the largest relative excess mortality is observed in younger patients.In early CKD,occlusive thrombotic coronary disease is common,but those who survive to reach end-stage renal failure requiring dialysis are more prone to sudden death attributable mostly to sudden arrhythmic events and heart failure related to left ventricular hypertrophy,coronary vascular calcification and electrolyte disturbances.In this review,we discuss the basis of the interaction of traditional risk factors for cardiovascular disease with various pathological processes such as endothelial dysfunction,oxidative stress,low grade chronic inflammation,neurohormonal changes and vascular calcification and stiffness which account for the structural and functional cardiac changes that predispose to excess morbidity and mortality in young people with CKD.展开更多
Objective： Vascular calcification is the consequence of the complex interaction between genetic, environmental, and vascular factors, which ultimately lead to the deposition of calcium in the tunica intima （atherosc...Objective： Vascular calcification is the consequence of the complex interaction between genetic, environmental, and vascular factors, which ultimately lead to the deposition of calcium in the tunica intima （atherosclerotic calcification） or tunica media （M6nckenberg＇s sclerosis）. Vascular calcification is also closely related to other pathologies, such as diabetes mellitus, dyslipidemia, and chronic kidney disease. It has been concluded that the degree of vascular calcification may vary from person to person, even if the associated pathologies and environmental factors are the same. Therefore, this suggests an important genetic contribution to the development of vascular calcification. This review aimed to find the most recent evidence about vascular calcification pathophysiology regarding the genetic aspects and molecular pathways. Data Sources： We conducted an exhaustive search in Scopus, EBSCO, and PubMed with the keywords ＂genetics and vascular calcification＂, ＂molecular pathways, genetic and vascular calcification＂ and included the main articles from January 1995 up to August 2016. We focused on the most recent evidence about vascular calcification pathophysiology regarding the genetic aspects and molecular pathways. Study Selection： The most valuable published original and review articles related to our objective were selected. Results： Vascular calcification is a multifactorial disease; thus, its pathophysiology cannot be explained by a single specific factor, rather than by the result of the association of several genetic variants, molecular pathway interactions, and environmental factors that promote its development. Conclusion： Although several molecular aspects of this mechanism have been elucidated, there is still a need for a better understanding of the factors that predispose to this disease.展开更多
The klotho gene has been identified as an aging suppressor that encodes a protein involved in cardiovascular disease （CVD）. The inac- tivation of the klotho gene causes serious systemic disorders resembling human ag...The klotho gene has been identified as an aging suppressor that encodes a protein involved in cardiovascular disease （CVD）. The inac- tivation of the klotho gene causes serious systemic disorders resembling human aging, such as atherosderosis, diffuse vascular calcification and shortened life span. Klotho has been demonstrated to ameliorate vascular endothelial dysfunction and delay vascular calcification. Fur- thermore, klotho gene polymorphisms in the human are associated with various cardiovascular events. Recent experiments show that klotho may reduce transient receptor potential canonical6 （TRPC6） channels, resulting in protecting the heart from hypertrophy and systolic dys- function. Fibroblast growth factor23 （FGF23） is a bone-derived hormone that plays an important role in the regulation of phosphate and vi- tamin D metabolism. FGF23 accelerates urinary phosphate excretion and suppresses 1,25-dihydroxy vitaminD3 （1,25（OH）2D3）synthesis in the presence ofFGF receptorl （FGFR1） and its co-receptor ldotho, principally in the kidney. The hormonal affects of circulating klotho pro- tein and FGF23 on vascular and heart have contributed to an understanding of their roles in the pathophysiology of arterial stiffness and left ventricular hypertrophy. Klotho and FGF23 appear to play a critical role in the pathogenesis of vascular disease, and may represent a novel potential therapeutic strategy for clinical intervention.展开更多
Aortic valve calcification disease (CAVD) is the most prevalent degenerative valve disease in humans, leading to significant morbidity and mortality. Despite its common occurrence, our understanding of the underlying ...Aortic valve calcification disease (CAVD) is the most prevalent degenerative valve disease in humans, leading to significant morbidity and mortality. Despite its common occurrence, our understanding of the underlying mechanisms remains incomplete, and available treatment options are limited and risky. A more comprehensive understanding of the biology of CAVD is essential to identify new therapeutic strategies. Animal models have played a crucial role in advancing our knowledge of CAVD and exploring potential treatments. However, these models have inherent limitations as they cannot fully replicate the complex physiological mechanisms of human CAVD. In this review, we examine various CAVD models ranging from pigs to mice, highlighting the unique characteristics of each model to enhance our understanding of CAVD. While these models offer valuable insights, they also have limitations and shortcomings. We propose that the guide wire model shows promise for future CAVD research, and streamlining the methodology could enhance our understanding and expand the research scope in this field.展开更多
文摘Insulin resistance is associated with subclinical vascular disease that is not justified by conventional cardiovascular risk factors,such as smoking or hypercholesterolemia.Vascular injury associated to insulin resistance involves functional and structural damage to the arterial wall that includes impaired vasodilation in response to chemical mediators,reduced distensibility of the arterial wall(arterial stiffness),vascular calcification,and increased thickness of the arterial wall.Vascular dysfunction associated to insulin resistance is present in asymptomatic subjects and predisposes to cardiovascular diseases,such as heart failure,ischemic heart disease,stroke,and peripheral vascular disease.Structural and functional vascular disease associated to insulin resistance is highly predictive of cardiovascular morbidity and mortality.Its pathogenic mechanisms remain undefined.Prospective studies have demonstrated that animal protein consumption increases the risk of developing cardiovascular disease and predisposes to type 2 diabetes(T2D)whereas vegetable protein intake has the opposite effect.Vascular disease linked to insulin resistance begins to occur early in life.Children and adolescents with insulin resistance show an injured arterial system compared with youth free of insulin resistance,suggesting that insulin resistance plays a crucial role in the development of initial vascular damage.Prevention of the vascular dysfunction related to insulin resistance should begin early in life.Before the clinical onset of T2D,asymptomatic subjects endure a long period of time characterized by insulin resistance.Latent vascular dysfunction begins to develop during this phase,so that patients with T2D are at increased cardiovascular risk long before the diagnosis of the disease.
文摘Cardiovascular disease poses the greatest risk of premature death seen among patients with chronic kidney disease(CKD).Up to 50% of mortality risk in the dialysis population is attributable to cardiovascular disease and the largest relative excess mortality is observed in younger patients.In early CKD,occlusive thrombotic coronary disease is common,but those who survive to reach end-stage renal failure requiring dialysis are more prone to sudden death attributable mostly to sudden arrhythmic events and heart failure related to left ventricular hypertrophy,coronary vascular calcification and electrolyte disturbances.In this review,we discuss the basis of the interaction of traditional risk factors for cardiovascular disease with various pathological processes such as endothelial dysfunction,oxidative stress,low grade chronic inflammation,neurohormonal changes and vascular calcification and stiffness which account for the structural and functional cardiac changes that predispose to excess morbidity and mortality in young people with CKD.
文摘Objective： Vascular calcification is the consequence of the complex interaction between genetic, environmental, and vascular factors, which ultimately lead to the deposition of calcium in the tunica intima （atherosclerotic calcification） or tunica media （M6nckenberg＇s sclerosis）. Vascular calcification is also closely related to other pathologies, such as diabetes mellitus, dyslipidemia, and chronic kidney disease. It has been concluded that the degree of vascular calcification may vary from person to person, even if the associated pathologies and environmental factors are the same. Therefore, this suggests an important genetic contribution to the development of vascular calcification. This review aimed to find the most recent evidence about vascular calcification pathophysiology regarding the genetic aspects and molecular pathways. Data Sources： We conducted an exhaustive search in Scopus, EBSCO, and PubMed with the keywords ＂genetics and vascular calcification＂, ＂molecular pathways, genetic and vascular calcification＂ and included the main articles from January 1995 up to August 2016. We focused on the most recent evidence about vascular calcification pathophysiology regarding the genetic aspects and molecular pathways. Study Selection： The most valuable published original and review articles related to our objective were selected. Results： Vascular calcification is a multifactorial disease; thus, its pathophysiology cannot be explained by a single specific factor, rather than by the result of the association of several genetic variants, molecular pathway interactions, and environmental factors that promote its development. Conclusion： Although several molecular aspects of this mechanism have been elucidated, there is still a need for a better understanding of the factors that predispose to this disease.
文摘The klotho gene has been identified as an aging suppressor that encodes a protein involved in cardiovascular disease （CVD）. The inac- tivation of the klotho gene causes serious systemic disorders resembling human aging, such as atherosderosis, diffuse vascular calcification and shortened life span. Klotho has been demonstrated to ameliorate vascular endothelial dysfunction and delay vascular calcification. Fur- thermore, klotho gene polymorphisms in the human are associated with various cardiovascular events. Recent experiments show that klotho may reduce transient receptor potential canonical6 （TRPC6） channels, resulting in protecting the heart from hypertrophy and systolic dys- function. Fibroblast growth factor23 （FGF23） is a bone-derived hormone that plays an important role in the regulation of phosphate and vi- tamin D metabolism. FGF23 accelerates urinary phosphate excretion and suppresses 1,25-dihydroxy vitaminD3 （1,25（OH）2D3）synthesis in the presence ofFGF receptorl （FGFR1） and its co-receptor ldotho, principally in the kidney. The hormonal affects of circulating klotho pro- tein and FGF23 on vascular and heart have contributed to an understanding of their roles in the pathophysiology of arterial stiffness and left ventricular hypertrophy. Klotho and FGF23 appear to play a critical role in the pathogenesis of vascular disease, and may represent a novel potential therapeutic strategy for clinical intervention.
文摘Aortic valve calcification disease (CAVD) is the most prevalent degenerative valve disease in humans, leading to significant morbidity and mortality. Despite its common occurrence, our understanding of the underlying mechanisms remains incomplete, and available treatment options are limited and risky. A more comprehensive understanding of the biology of CAVD is essential to identify new therapeutic strategies. Animal models have played a crucial role in advancing our knowledge of CAVD and exploring potential treatments. However, these models have inherent limitations as they cannot fully replicate the complex physiological mechanisms of human CAVD. In this review, we examine various CAVD models ranging from pigs to mice, highlighting the unique characteristics of each model to enhance our understanding of CAVD. While these models offer valuable insights, they also have limitations and shortcomings. We propose that the guide wire model shows promise for future CAVD research, and streamlining the methodology could enhance our understanding and expand the research scope in this field.
