Carotid artery atherosclerosis in hypertensive patients with a functional LDL receptor-related protein 6 gene variant

Sarzani, Riccardo; Salvi, F.; Bordicchia, Marica; Guerra, Federico; Battistoni, Ilaria; Pagliariccio, Gabriele; Carbonari, Luciano; Dessı̀-Fulgheri, Paolo; Rappelli, A

doi:10.1016/j.numecd.2009.08.004

Cited by 57 publications

(49 citation statements)

References 29 publications

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“…Indeed, LRP6 mutations in humans are associated with accelerated development of atherosclerosis (148,215). The trait of hyperlipidemia associated with these mutations is rescued by administration of Wnt3a in mice by altering the expression levels of hepatic lipogenic enzymes (78).…”

Section: Lrp Receptors and The Development Of Atherosclerosismentioning

confidence: 99%

Wnt Signaling in Cardiac Disease

Hermans

Blankesteijn

2015

Comprehensive Physiology

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Wnt signaling encompasses multiple and complex signaling cascades and is involved in many developmental processes such as tissue patterning, cell fate specification, and control of cell division. Consequently, accurate regulation of signaling activities is essential for proper embryonic development. Wnt signaling is mostly silent in the healthy adult organs but a reactivation of Wnt signaling is generally observed under pathological conditions. This has generated increasing interest in this pathway from a therapeutic point of view. In this review article, the involvement of Wnt signaling in cardiovascular development will be outlined, followed by its implication in myocardial infarct healing, cardiac hypertrophy, heart failure, arrhythmias, and atherosclerosis. The initial experiments not always offer consensus on the effects of activation or inactivation of the pathway, which may be attributed to (i) the type of cardiac disease, (ii) timing of the intervention, and (iii) type of cells that are targeted. Therefore, more research is needed to determine the exact implication of Wnt signaling in the conditions mentioned above to exploit it as a powerful therapeutic target.

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Section: Lrp Receptors and The Development Of Atherosclerosismentioning

confidence: 99%

Wnt Signaling in Cardiac Disease

Hermans

Blankesteijn

2015

Comprehensive Physiology

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“…The rare gene variant 611C was associated with hypertension, metabolic abnormalities, and early coronary artery disease. Moreover, also the more common LRP6 variant 1062 V associates strongly with the presence of coronary artery disease in hypertensive patients [61].…”

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confidence: 99%

From skeletal to cardiovascular disease in 12 steps—the evolution of sclerostin as a major player in CKD-MBD

et al. 2015

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Canonical Wnt signaling activity contributes to physiological and adaptive bone mineralization and is an essential player in bone remodeling. Sclerostin is a prototypic soluble canonical Wnt signaling pathway inhibitor that is produced in osteocytes and blocks osteoblast differentiation and function. Therefore, sclerostin is a potent inhibitor of bone formation and mineralization. Accordingly, rodent sclerostin-deficiency models exhibit a strong bone phenotype. Moreover, blocking sclerostin represents a promising treatment perspective against osteoporosis. Beyond the bone field novel data definitely associate Wnt signaling in general and sclerostin in particular with ectopic extraosseous mineralization processes, as is evident in cardiovascular calcification or calciphylaxis. Uremia is characterized by parallel occurrence of disordered bone mineralization and accelerated cardiovascular calcification (chronic kidney disease - mineral and bone disorder, CKD-MBD), linking skeletal and cardiovascular disease-the so-called bone-vascular calcification paradox. In consequence, sclerostin may qualify as an emerging player in CKD-MBD. We present a stepwise review approach regarding the rapidly evolving field sclerostin participation in CKD-MBD. Starting from data originating in the classical bone field we look separately at three major areas of CKD-MBD: disturbed mineral metabolism, renal osteodystrophy, and uremic cardiovascular disease. Our review is intended to help the nephrologist revise the potential importance of sclerostin in CKD by focusing on how sclerostin research is gradually evolving from the classical osteoporosis niche into the area of CKD-MBD. In particular, we integrate the limited amount of available data in the context of pediatric nephrology.

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“…Thus, hypertensive patients with this mutation may need some clinical checkment to detect subclinical atherosclerosis. 23 Besides, LRP6 rs2302685, predisposing people toward early-onset ileal Crohn's disease, may also turn into an attractive therapeutic target as an alternative to the current anti-inflammatory approaches in the therapy of Crohn' diseases. 80 Another variant, LRP6 rs6488507, may be associated with the increased risk of NSCLC in tobacco smokers, and thus the clinical diagnostic testing may be necessary for carriers with smoking history.…”

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

“…20 According to the surveys, the morbidity of metabolic syndrome among American and Chinese is 34 and 23.3%, respectively. 21,22 Indeed, numerous reports confirmed that mutants of LRP6 and TCF7L2 caused atherosclerosis, 23 diabetes, 24 hyperlipidemia 23,25 and hypertension. 26 Recently, attenuation of Wnt-mediated transcription resulting from mutations in LRP6 has been genetically linked to coronary artery disease (CAD) as well as several features of metabolic syndrome including hyperlipidemia, hypertension and diabetes but not obesity.…”

mentioning

confidence: 98%