Vascular remodeling contributes to end-organ damage in hypertension, providing a rationale for regression of remodeling of blood vessels as a therapeutic aim.
Full Answer
What is the role of vascular remodeling in hypertension (high blood pressure)?
In hypertension, vascular remodeling contributes to increased peripheral resistance, impacting both development and complications of hypertension.
What is the pathophysiology of vascular remodeling?
Vascular remodeling is a complex pathophysiological process that plays a major role in the clinical manifestations of cardiovascular diseases. Vascular remodeling is a complex process that involves physical, biochemical and genetic components.
Is remodeling an adaptive or maladaptive approach to hypertension?
Remodeling may initially be adaptive but eventually becomes maladaptive and compromises organ function, contributing to cardiovascular complications of hypertension.
How does blood pressure affect vascular structure?
Research focused on new signaling pathways and molecules that can participate in the mechanisms of vascular remodeling has provided evidence showing that vascular structure is not only affected by blood pressure, but also by mechanisms that are independent of the increased pressure.
What is the importance of remodeling the vascular system?
What is vascular remodeling?
What is the effect of vascular remodeling in PAH?
What is the function of VSMCs?
What is the process of altering structure and arrangement in blood vessels?
How does vascular remodeling affect a pregnancy?
What is the role of vasoactive substances in vascular remodeling?
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About this website
Does hypertension cause vascular Remodelling?
Growth, apoptosis, inflammation, and fibrosis contribute to vascular remodeling in hypertension.
How does HBP affect the artery walls?
Damage to the arteries High blood pressure (hypertension) gradually increases the pressure of blood flowing through the arteries. Hypertension may cause: Damaged and narrowed arteries. High blood pressure can damage the cells of the arteries' inner lining.
How does hypertension affect the structural integrity of blood vessel walls?
More elastic vessels, such as the aorta, attenuate the effects of hypertension initially by way of remodelling, but prolonged hypertension in these large elastic arteries and particularly in less elastic vessels (such as smaller arteries and veins) tends to alter the vessel wall shape and composition, ultimately ...
What causes vascular Remodelling?
Inflammation, vascular injury, oxidative stress, and hemodynamics are the most important drivers of vascular remodeling and are thought to play an important role in regulation of MMP production and activity. Vascular injury of the arterial wall upregulated MMP activity.
Can you repair damage from high blood pressure?
Treating out-of-control blood pressure with antihypertensive medication can greatly reduce your risk for heart attack, stroke and heart failure, but the current approach to treatment can't undo all of the previous damage or restore cardiovascular disease risk to ideal levels, a new Northwestern Medicine study suggests.
What damage is done by high blood pressure?
Left undetected or uncontrolled, high blood pressure can lead to: Heart attack — High blood pressure damages arteries that can become blocked and prevent blood flow to the heart muscle. Stroke — High blood pressure can cause blood vessels that supply blood and oxygen to the brain to become blocked or burst.
How does hypertension affect the circulatory system?
High blood pressure can damage your arteries by making them less elastic, which decreases the flow of blood and oxygen to your heart and leads to heart disease. In addition, decreased blood flow to the heart can cause: Chest pain, also called angina.
How does hypertension damage endothelium?
Several investigators have reported possible mechanisms of impairment of endothelial function in hypertension: increase in amount of the endogenous eNOS inhibitor asymmetrical dimethylarginine, increases in amounts of vasoconstrictors, such as Ang II, endothelin-1 and norepinephrine, and inactivation of NO by ROS.
Why does hypertension increase risk of atherosclerosis?
High blood pressure can damage your blood vessel walls. Fats in the blood can collect in these damaged areas, clogging up the arteries and leading to atherosclerosis – where the arteries become narrow and stiff, reducing the blood flow around your body.
What causes vascular remodeling in pulmonary hypertension?
Experimentally, the TH-2 inflammation leads to increased transforming growth factor (TGF)-β1 (Kumar et al. 2015), which ultimately trigger pulmonary artery remodeling and PH. This process is largely dependent of thrombospondin-1 producing blood marrow monocytes (Kumar et al, unpublished).
Is vascular Remodelling a normal physiological response?
Vascular Remodeling and Acute Phase Reactants. The production of acute phase reactants is a normal physiological response to cytokine release in acute and chronic inflammatory conditions.
Is pulmonary arterial hypertension the same as high blood pressure?
Having pulmonary arterial hypertension (PAH) means that you have high blood pressure in the arteries that go from your heart to your lungs . It's different from having regular high blood pressure. With PAH, the tiny arteries in your lungs become narrow or blocked.
Vascular remodeling: mechanisms and implications - PubMed
It is now recognized that, in addition to being able to change its tone acutely, the blood vessel is capable of altering its structure chronically in response to specific conditions. This is mediated by vascular remodeling, an active process that results in a change in the geometry of the blood vess …
Vascular Remodeling in Health and Disease | SpringerLink
The term vascular remodeling is commonly used to define the structural changes in blood vessel geometry that occur in response to long-term physiologic alterations in blood flow or in response to vessel wall injury brought about by trauma or underlying cardiovascular diseases.1–4 The process of remodeling, which begins as an adaptive response to long-term hemodynamic alterations such as ...
Mouse Model of Wire Injury-Induced Vascular Remodeling
Neointima hyperplasia is known to form in the damaged vasculature caused by vascular grafting (vein to arterial) [1, 2] and interventional catheter treatment of coronary and peripheral artery atherosclerotic occlusions [3, 4].To prevent postangioplasty restenosis, neointima formation has been intensively investigated in animal models including the mouse (Part 1, Re-Stenosis Models After ...
How does antihypertensive therapy affect the vascular wall?
Antihypertensive agents may affect the vascular wall directly and indirectly, the latter resulting from effects of BP lowering. Reduction of BP shifts stress of the wall to the more compliant segment of the stress/strain relationship, so that more elastin and less collagen determine vascular stiffness. Collagen linking to VSMCs and the degree of tensing of the collagen jacket play important roles, because collagen contributes to stiffness of the vessel wall in the latter portion of the stress/strain curve, as collagen fibers may be coiled and not under tension until the VSMCs in series and elastin in parallel have been stretched.
Does a blockade of the renin-angiotensin system improve vascular structure and function
The mechanisms whereby blockade of the renin-angiotensin system improves vascular structure and function probably result from inhibition of growth-promoting, pro-oxidant, and proinflammatory actions of Ang II. 73 Vasodilatation has also been considered to play a role, 74 because vasoconstriction may lead to small artery remodeling, 21 and vasodilatation, through changes in flow, modulates vascular remodeling. 75 Atenolol induces peripheral vasoconstriction, 76 which could explain its inability to improve vascular remodeling, 43 – 49 whereas agents that improve remodeling, like ACEIs, ARBs, or CCBs, are vasodilators.
What is the importance of remodeling the vascular system?
Remodeling the Vasculature, Extracellular Matrix, and Immune System. Vascular remodeling is critical in a system such as the endometrium in which rapid , cyclic growth and regression occur , and the endometrium is a rich source of angiogenic factors in both pregnant and nonpregnant states.
What is vascular remodeling?
Vascular remodeling is a complex process that involves physical, biochemical and genetic components. Biological and physiological studies have greatly elucidated the mechanisms by which VSMC undergo phenotypic modulation and promote neointima formation. As genetic technologies advance, this already large body of literature will expand. While our understanding of the genetic basis of vascular remodeling increases, the future challenges will require systems biology approaches. Specifically, gene profiling now enables the transcriptome to be analyzed and mass spectrometry enables the proteome to be characterized. However, many diseases involve complex interactions among proteins mediated by post-translational modifications (e.g., acylation, glycation, nitrosylation, oxidation, phosphorylation, SUMOylation, ubiquitination). Finally, alterations in key metabolic products (the metabolome) play critical roles in the vasculature. Furthermore, alterations in ECM and cell–cell interactions within the wall are critical determinants of vascular remodeling. It is likely that recruitment of pluripotent stem cells also contributes to vascular remodeling. In summary, our understanding of the multiple mechanisms involved in VSMC vascular remodeling should facilitate development of therapies to treat aneurysms, atherosclerosis, and restenosis.
What is the effect of vascular remodeling in PAH?
Pulmonary vascular remodeling in PAH involves increased production of ECM, including collagen, elastin, fibronectin, and tenascin, a matrix glycoprotein that amplifies the proliferative response of SMCs to growth factors. The internal elastic lamina, which separates the endothelium from SMCs in muscular arteries, is fragmented in PAH. Rabinovitch67 speculates that endothelial injury causes a loss of its barrier function and allows leakage of a serum factor into the normally isolated subendothelium. This serum factor could induce activity of endogenous vascular elastase or matrix metalloproteinases with release of matrix-bound SMC mitogens. The result is smooth muscle hypertrophy and proliferation and increased synthesis of connective tissue proteins and tenascin. Tenascin then contributes to the differentiation of precursor cells into the SMCs that appear in the normally nonmuscular, small peripheral PAs, and causes hypertrophy in muscularized arteries. In vitro administration of elastase and matrix metalloproteinase inhibitors to pulmonary arteries from pulmonary hypertensive animals lowered tenascin levels, induced apoptosis of SMCs, and reversed PH-associated remodeling with a reduction in ECM components. 67 In a rat model, an elastase inhibitor was also shown to reverse pulmonary vascular disease completely, with normalization of pulmonary artery pressure, apoptosis, and resorption of the ECM with regression of the hypertrophied vessel wall. 68
What is the function of VSMCs?
VSMCs produce an endogenous vascular elastase in response to serum factors. Serine elastases can activate matrix metalloproteinases (MMPs) and repress tissue inhibitors of MMPs (TIMPs). VSMCs express collagenases MMP 1 and 3 and gelatinases MMP 2 and 9. MMP-2 expression and activity are increased in experimental PAH.
What is the process of altering structure and arrangement in blood vessels?
Vascular remodeling is the process of altering structure and arrangement in blood vessels through cell growth, cell death, cell migration, and production or degradation of the ECM. Inflammation, vascular injury, oxidative stress, and hemodynamics are the most important drivers of vascular remodeling and are thought to play an important role in ...
How does vascular remodeling affect a pregnancy?
Vascular remodeling is an essential process for a successful pregnancy. Blood flow must increase to the uterus to provide nutrients and oxygen for the fetus. This occurs via vasculogenesis and angiogenesis, increase in diameter and length of spiral arteries, and ultimately invasion of maternal blood vessels by embryonic cells. Lack of remodeling can lead to diseases such as intrauterine growth restriction. However, this vascular remodeling must be regulated, as too much blood flow can lead to oxidative damage to the embryo or to hemorrhage. This finely tuned homeostatic regulation of vascular remodeling is accomplished via a variety of signaling pathways that have capacity for pro- and/or antiangiogenic actions. While much research has been done on this topic, there are still many questions remaining, and novel regulators are still being identified. In this chapter, the MAS-related gene family and uterine hemoglobin biosynthesis were introduced as additional components involved in regulating vascular dynamics and oxygen/nutrient provision to the developing embryo. Understanding the role of the various regulators of vascular dynamics will provide further insight into the etiologies and treatment of miscarriage, preeclampsia, intrauterine growth restriction, and other disorders of uterine vascular remodeling.
What is the role of vasoactive substances in vascular remodeling?
The pivotal role of vasoactive substances present in the blood vessel in the control of vascular growth is well known. Whereas vasoconstricting peptides such as Ang II promote vascular growth, vasodilating substances such as natriuretic peptides inhibit vascular growth. ANP has been shown to be antimitogenic in endothelial and vascular smooth muscle cells133,149,150 and to attenuate the growth response to adrenergic stimuli 151 and induce apoptosis in neonatal rat cardiomyocytes. 152 Moreover, ANP-induced apoptosis occurs through the induction of p53 and inhibition of Bc12 proteins. 153 The apoptotic effect of ANP can be inhibited by specific blockade of NPR-A or modulated by ET (an antiapoptotic factor). Similar effects have been noted in neonatal rat cardiac myocytes. 152
Infinite Insults
There are over 400 known “insults” to the cardiovascular system. These are things like hyperlipidemia, inflammation, acute and chronic infections, elevated homocysteine, elevated ferritin, heavy metals, poor diet, and the list goes on. Your body recognizes these insults as a threat and mounts a response or defense against them.
3 Finite Responses
The body recognizes the insult or attack and mounts a response in one of three ways: Inflammation, Oxidative Stress, and Vascular Immune Function. While these are 3 separate responses, they are all linked and activation of one of them usually also stimulates the other two.
What is the importance of remodeling the vascular system?
Remodeling the Vasculature, Extracellular Matrix, and Immune System. Vascular remodeling is critical in a system such as the endometrium in which rapid , cyclic growth and regression occur , and the endometrium is a rich source of angiogenic factors in both pregnant and nonpregnant states.
What is vascular remodeling?
Vascular remodeling is a complex process that involves physical, biochemical and genetic components. Biological and physiological studies have greatly elucidated the mechanisms by which VSMC undergo phenotypic modulation and promote neointima formation. As genetic technologies advance, this already large body of literature will expand. While our understanding of the genetic basis of vascular remodeling increases, the future challenges will require systems biology approaches. Specifically, gene profiling now enables the transcriptome to be analyzed and mass spectrometry enables the proteome to be characterized. However, many diseases involve complex interactions among proteins mediated by post-translational modifications (e.g., acylation, glycation, nitrosylation, oxidation, phosphorylation, SUMOylation, ubiquitination). Finally, alterations in key metabolic products (the metabolome) play critical roles in the vasculature. Furthermore, alterations in ECM and cell–cell interactions within the wall are critical determinants of vascular remodeling. It is likely that recruitment of pluripotent stem cells also contributes to vascular remodeling. In summary, our understanding of the multiple mechanisms involved in VSMC vascular remodeling should facilitate development of therapies to treat aneurysms, atherosclerosis, and restenosis.
What is the effect of vascular remodeling in PAH?
Pulmonary vascular remodeling in PAH involves increased production of ECM, including collagen, elastin, fibronectin, and tenascin, a matrix glycoprotein that amplifies the proliferative response of SMCs to growth factors. The internal elastic lamina, which separates the endothelium from SMCs in muscular arteries, is fragmented in PAH. Rabinovitch67 speculates that endothelial injury causes a loss of its barrier function and allows leakage of a serum factor into the normally isolated subendothelium. This serum factor could induce activity of endogenous vascular elastase or matrix metalloproteinases with release of matrix-bound SMC mitogens. The result is smooth muscle hypertrophy and proliferation and increased synthesis of connective tissue proteins and tenascin. Tenascin then contributes to the differentiation of precursor cells into the SMCs that appear in the normally nonmuscular, small peripheral PAs, and causes hypertrophy in muscularized arteries. In vitro administration of elastase and matrix metalloproteinase inhibitors to pulmonary arteries from pulmonary hypertensive animals lowered tenascin levels, induced apoptosis of SMCs, and reversed PH-associated remodeling with a reduction in ECM components. 67 In a rat model, an elastase inhibitor was also shown to reverse pulmonary vascular disease completely, with normalization of pulmonary artery pressure, apoptosis, and resorption of the ECM with regression of the hypertrophied vessel wall. 68
What is the function of VSMCs?
VSMCs produce an endogenous vascular elastase in response to serum factors. Serine elastases can activate matrix metalloproteinases (MMPs) and repress tissue inhibitors of MMPs (TIMPs). VSMCs express collagenases MMP 1 and 3 and gelatinases MMP 2 and 9. MMP-2 expression and activity are increased in experimental PAH.
What is the process of altering structure and arrangement in blood vessels?
Vascular remodeling is the process of altering structure and arrangement in blood vessels through cell growth, cell death, cell migration, and production or degradation of the ECM. Inflammation, vascular injury, oxidative stress, and hemodynamics are the most important drivers of vascular remodeling and are thought to play an important role in ...
How does vascular remodeling affect a pregnancy?
Vascular remodeling is an essential process for a successful pregnancy. Blood flow must increase to the uterus to provide nutrients and oxygen for the fetus. This occurs via vasculogenesis and angiogenesis, increase in diameter and length of spiral arteries, and ultimately invasion of maternal blood vessels by embryonic cells. Lack of remodeling can lead to diseases such as intrauterine growth restriction. However, this vascular remodeling must be regulated, as too much blood flow can lead to oxidative damage to the embryo or to hemorrhage. This finely tuned homeostatic regulation of vascular remodeling is accomplished via a variety of signaling pathways that have capacity for pro- and/or antiangiogenic actions. While much research has been done on this topic, there are still many questions remaining, and novel regulators are still being identified. In this chapter, the MAS-related gene family and uterine hemoglobin biosynthesis were introduced as additional components involved in regulating vascular dynamics and oxygen/nutrient provision to the developing embryo. Understanding the role of the various regulators of vascular dynamics will provide further insight into the etiologies and treatment of miscarriage, preeclampsia, intrauterine growth restriction, and other disorders of uterine vascular remodeling.
What is the role of vasoactive substances in vascular remodeling?
The pivotal role of vasoactive substances present in the blood vessel in the control of vascular growth is well known. Whereas vasoconstricting peptides such as Ang II promote vascular growth, vasodilating substances such as natriuretic peptides inhibit vascular growth. ANP has been shown to be antimitogenic in endothelial and vascular smooth muscle cells133,149,150 and to attenuate the growth response to adrenergic stimuli 151 and induce apoptosis in neonatal rat cardiomyocytes. 152 Moreover, ANP-induced apoptosis occurs through the induction of p53 and inhibition of Bc12 proteins. 153 The apoptotic effect of ANP can be inhibited by specific blockade of NPR-A or modulated by ET (an antiapoptotic factor). Similar effects have been noted in neonatal rat cardiac myocytes. 152