Future Treatment of Hypertension: Shifting the Focus from Blood Pressure Lowering to Arterial Stiffness Modulation?

Fok, Henry; Cruickshank, J.

doi:10.1007/s11906-015-0569-6

Cited by 25 publications

(23 citation statements)

References 144 publications

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“…The phenomena that causes the stiffening in relation to high blood pressure is unknown, but this finding reinforces previously reported links between HTN and the gastrointestinal system. In HTN, it has been proposed that the focus should be shifted from lowering arterial blood pressure to altering the remodeling of vascular smooth muscle cells [45]. Our data indicate that abnormal smooth muscle cell activity may be present in other organs as well, which reinforces the need for systemic approaches to understanding HTN that go beyond the cardiovascular system.…”

Section: Discussionsupporting

confidence: 69%

Hypertension-linked mechanical changes of rat gut

et al. 2016

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Hypertension is the most prevalent risk factor for cardiovascular disease caused by a persistent increase in arterial blood pressure that has lasting effects on the mechanical properties of affected tissues like myocardium and blood vessels. Our group recently discovered that gut dysbiosis is linked to hypertension in several animal models and humans; however, whether hypertension influences the gut’s mechanical properties remains unknown. In this study, we evaluated the hypothesis that hypertension increases fibrosis and thus mechanical properties of the gut. A custom indentation system was used to test colon samples from Wistar Kyoto (WKY) normotensive rats and Spontaneously Hypertensive Rats (SHR). Using force-displacement data, we derived an steady-state modulus metric to quantify mechanical properties of gastrointestinal tissue. We observed that SHR proximal colon has a mean steady-state modulus almost 3 times greater than WKY control rat colon (5.11 ± 1.58 kPa and 18.17 ± 11.45 kPa, respectively). These increases were associated with increase in vascular smooth muscle cells layer and collagen deposition in the intestinal wall in the SHR.

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Section: Discussionsupporting

confidence: 69%

Hypertension-linked mechanical changes of rat gut

et al. 2016

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“…Of note, similar regulatory circuits likely function during development [97]. Thus, augmenting VSM noncanonical Wnt signals results in VSM plasticity, de-differentiation and an arteriosclerotic tissue phenotype [27] – thereby increasing myocardial workload, impairing Windkessel physiology necessary for smooth distal tissue perfusion and causing cardiovascular dysfunction[98, 99]. …”

Section: Introductionmentioning

confidence: 99%

Wnt signaling in cardiovascular disease: opportunities and challenges

Towler¹

2017

Current Opinion in Lipidology

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Purpose of review Cardiometabolic diseases increasingly afflict our aging, dysmetabolic citizenry. Complex signals regulating low density lipoprotein receptor-related protein (LRP) and frizzled protein family members – the plasma membrane receptors for the cadre of Wnt polypeptide morphogens – contribute to the control of cardiovascular homeostasis. Recent findings Both canonical (β-catenin-dependent) and noncanonical (β-catenin-independent) Wnt signaling programs control vascular smooth muscle cell (VSM) phenotypic modulation in cardiometabolic disease. LRP6 limits VSM proliferation, reduces arteriosclerotic transcriptional reprogramming, and preserves insulin sensitivity while LRP5 restrains foam cell formation. Adipose, skeletal muscle, macrophages and VSM have emerged as important sources of circulating Wnt ligands that are dynamically regulated during the prediabetes-diabetes transition with cardiometabolic consequences. Platelets release Dkk1, an LRP5/LRP6 inhibitor that induces endothelial inflammation and the prosclerotic endothelial-mesenchymal transition. By contrast, inhibitory secreted frizzled-related proteins shape the Wnt signaling milieu to limit myocardial inflammation with ischemia-reperfusion injury. VSM sclerostin, an inhibitor of canonical Wnt signaling in bone, restrains remodeling that predisposes to aneurysm formation, and is down-regulated in aneurysmal vessels by epigenetic methylation. Summary Components of the Wnt signaling cascade represent novel targets for pharmacological intervention in cardiometabolic disease. Conversely, strategies targeting the Wnt signaling cascade for other therapeutic purposes will have cardiovascular consequences that must be delineated to establish clinically useful pharmacokinetic – pharmacodynamic relationships.

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“…Arterial stiffness as a measure of distensibility and compliance of vessels is an established marker of cardiovascular morbidity and mortality and therefore a potential therapeutic target12. Arterial hypertension and aging are established factors contributing to arterial stiffness and the role of inflammation in decreasing vascular compliance is becoming more evident as well34.…”

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confidence: 99%

Mean Platelet Volume and Arterial Stiffness – Clinical Relationship and Common Genetic Variability

Panova‐Noeva

Arnold

Hermanns

et al. 2017

Sci Rep

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Vessel wall stiffening is an important clinical parameter, but it is unknown whether platelets, key elements in the pathogenesis of arterial thrombosis, are associated with arterial stiffness. The present studies sought to determine whether mean platelet volume (MPV), a potential marker of platelet activation, is linked to vascular elasticity as assessed by the augmentation index (AIx), in 15,010 individuals from the population-based Gutenberg Health Study. Multivariable analysis showed that MPV in both males (β 0.776; 95thCI [0.250;1.16]; p = 0.0024) and females (β 0.881[0.328;1.43]; p = 0.0018) is strongly associated with AIx. Individuals with MPV and AIx above the sex-specific medians had worse survival. Association analysis between MPV-related genetic variants and arterial stiffness identified four genetic variants in males and one in females related with AIx. Cox regression analysis for mortality identified one of these joint genetic variants close to ring finger protein 145 gene (RNF145, rs10076782) linked with increased mortality (hazard ratio 2.02; 95thCI [1.35;3.02]; p = 0.00061). Thus, these population-based data demonstrate a close relation between platelet volume as a potential marker of platelet activation and arterial stiffness in both sexes. Further research is warranted to further elucidate the mechanisms underlying larger platelets‘ role in arterial stiffening including the role of shared common genetics.

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Future Treatment of Hypertension: Shifting the Focus from Blood Pressure Lowering to Arterial Stiffness Modulation?

Cited by 25 publications

References 144 publications

Hypertension-linked mechanical changes of rat gut

Hypertension-linked mechanical changes of rat gut

Wnt signaling in cardiovascular disease: opportunities and challenges

Mean Platelet Volume and Arterial Stiffness – Clinical Relationship and Common Genetic Variability

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