Structural Alterations of Subcutaneous Small-Resistance Arteries May Predict Major Cardiovascular Events in Patients With Hypertension

DeCiuceis, Carolina; Porteri, Enzo; Rizzoni, Damiano; Rizzardi, Nicola; Paiardi, Silvia; Boari, Gianluca E.M.; Miclini, Marco; Zani, F.; Muiesan, María Lorenza; Donato, Filippo

doi:10.1016/j.amjhyper.2007.03.016

Cited by 131 publications

(76 citation statements)

References 29 publications

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“…Skin circulation also is altered in a number of disease states, including renal disease (2), hypercholesterolemia (3), peripheral vascular disease (4), heart failure, and hypertension (5). Identification of structural alterations to the subcutaneous microvasculature provides a powerful prognostic tool to predict cardiovascular events in hypertensive patients (6), and impaired microvascular vasodilation and capillary rarefaction is associated with familial predisposition to hypertension (7).…”

Section: Hif-alpha | Arginase | Vascular Tonementioning

confidence: 99%

HIF isoforms in the skin differentially regulate systemic arterial pressure

Cowburn

Takeda²,

Boutin³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Vascular flow through tissues is regulated via a number of homeostatic mechanisms. Localized control of tissue blood flow, or autoregulation, is a key factor in regulating tissue perfusion and oxygenation. We show here that the net balance between two hypoxia-inducible factor (HIF) transcription factor isoforms, HIF-1α and HIF-2α, is an essential mechanism regulating both local and systemic blood flow in the skin of mice. We also show that balance of HIF isoforms in keratinocyte-specific mutant mice affects thermal adaptation, exercise capacity, and systemic arterial pressure. The two primary HIF isoforms achieve these effects in opposing ways that are associated with HIF isoform regulation of nitric oxide production. We also show that a correlation exists between altered levels of HIF isoforms in the skin and the degree of idiopathic hypertension in human subjects. Thus, the balance between HIF-1α and HIF-2α expression in keratinocytes is a control element of both tissue perfusion and systemic arterial pressure, with potential implications in human hypertension.HIF-alpha | arginase | vascular tone A utoregulation of vascular flow in peripheral tissues is essential both for controlling local tissue perfusion and for the regulation of systemic blood pressure. This dual role for peripheral blood flow is dependent in turn on a range of factors that act to adjust local vascular tone. A key element of this control is the balance between O 2 demand and O 2 supply (1). This balance causes increased need for oxygen to induce increased blood flow. This regulatory pathway in peripheral tissues has a direct impact on systemic arterial pressure, because peripheral vascular resistance in large part determines total vascular resistance in the arterial bed.The skin contains a very extensive series of vascular plexi. This vascular bed has a range of essential functions, which include regulating body temperature. Skin circulation also is altered in a number of disease states, including renal disease (2), hypercholesterolemia (3), peripheral vascular disease (4), heart failure, and hypertension (5). Identification of structural alterations to the subcutaneous microvasculature provides a powerful prognostic tool to predict cardiovascular events in hypertensive patients (6), and impaired microvascular vasodilation and capillary rarefaction is associated with familial predisposition to hypertension (7).The heterodimeric transcription factors hypoxia-inducible factoralpha (HIF-1α) and HIF-2α are essential for the maintenance of cellular oxygen homeostasis (8). In response to hypoxia, stabilized HIF-1α and HIF-2α proteins initiate the expression of genes that alleviate hypoxic stress, including genes promoting cell growth, adhesion, and migration, new vessel formation, and the development of vascular networks (9,10).Recent data from a number of groups have indicated that HIF-1α and HIF-2α can act in a dualistic manner to regulate a range of responses in vivo; these interactions include functionally opposing interactions with the Myc t...

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Section: Hif-alpha | Arginase | Vascular Tonementioning

confidence: 99%

HIF isoforms in the skin differentially regulate systemic arterial pressure

Cowburn

Takeda²,

Boutin³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…This parameter is widely used in resistance-sized arteries structural analysis and its increment has been related to an increased risk of cardiovascular disease in hypertensive patients [20][21].…”

Section: Discussionmentioning

confidence: 99%

“…Hypoxia, in turn, is a condition that activates angiogenic genes, such as HIF, which further stimulate the formation of new vessels [20].…”

Section: Discussionmentioning

confidence: 99%

Resistance-Sized Arteries Structure and Capillary Density Changes in Glioblastoma and Meningioma Peritumoral Brain Tissue

Boari¹

2013

J Neurol Disord

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“…There are now numerous studies which support the notion that changes in small artery structure have strong prognostic significance in hypertensive patients, over and above all other known cardiovascular risk factors (Rizzoni et al, 2003;De Ciuceis et al, 2007;Mathiassen, Buus, et al, 2007b). Understanding the mechanisms which may modulate resistance arterial eutrophic remodelling is thus important, but these remain poorly understood.…”

Section: Resistance Artery Structure and Hypertensionmentioning

confidence: 99%

Plasma membrane calcium ATPases (PMCAs) as potential targets for the treatment of essential hypertension

Little

Cartwright

Neyses

et al. 2016

Pharmacology & Therapeutics

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The incidence of hypertension, the major modifiable risk factor for cardiovascular disease, is increasing. Thus, there is a pressing need for the development of new and more effective strategies to prevent and treat hypertension. Development of these relies on a continued evolution of our understanding of the mechanisms which control blood pressure (BP). Resistance arteries are important in the regulation of total peripheral resistance and BP; changes in their structure and function are strongly associated with hypertension. Anti-hypertensives which both reduce BP and reverse changes in resistance arterial structure reduce cardiovascular risk more than therapies which reduce BP alone. Hence, identification of novel potential vascular targets which modify BP is important. Hypertension is a multifactorial disorder which may include a genetic component. Genome wide association studies have identified ATP2B1, encoding the calcium pump plasma membrane calcium ATPase 1 (PMCA1), as having a strong association with BP and hypertension. Knockdown or reduced PMCA1 expression in mice has confirmed a physiological role for PMCA1 in BP and resistance arterial regulation. Altered expression or inhibition of PMCA4 has also been shown to modulate these parameters. The mechanisms whereby PMCA1 and 4 can modulate vascular function remain to be fully elucidated but may involve regulation of intracellular calcium homeostasis and/or comprise a structural role. However, clear physiological links between PMCA and BP, coupled with experimental studies directly linking PMCA1 and 4 to changes in BP and arterial function, suggest that they may be important targets for the development of new pharmacological modulators of BP.

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Structural Alterations of Subcutaneous Small-Resistance Arteries May Predict Major Cardiovascular Events in Patients With Hypertension

Abstract: Structural alterations of small-resistance arteries may predict FCE and SMI. The prognostic role of small-resistance artery structure also applies to medium-risk patients with essential hypertension, at least when MCEs are included in the analysis.

Cited by 131 publications

References 29 publications

HIF isoforms in the skin differentially regulate systemic arterial pressure

HIF isoforms in the skin differentially regulate systemic arterial pressure

Resistance-Sized Arteries Structure and Capillary Density Changes in Glioblastoma and Meningioma Peritumoral Brain Tissue

Plasma membrane calcium ATPases (PMCAs) as potential targets for the treatment of essential hypertension

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