Collagen Metabolism in Extracellular Matrix May Be Involved in Arterial Stiffness in Older Hypertensive Patients with Left Ventricular Hypertrophy

Ishikawa, Joji; Kario, Kazuomi; Matsui, Yoshio; Shibasaki, Seiichi; Morinari, Masato; Kaneda, Ruri; Hoshide, Satoshi; Eguchi, Kazuo; Hojo, Yukihiro; Shimada, Kazuyuki

doi:10.1291/hypres.28.995

Cited by 44 publications

(42 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Abnormal collagen metabolism has been involved in arterial stiffness (Ishikawa et al, 2005), a risk factor for arteriosclerosis, arterial and pulmonary hypertension (Gong et al, 2004). Similar observations have been reported for fibroblasts through a post-transcriptional mechanism (Horino et al, 2002).…”

Section: Impact Of Hypoxia On Ecm Remodelingmentioning

confidence: 61%

Influence of stress on extracellular matrix and integrin biology

et al. 2011

View full text Add to dashboard Cite

Section: Impact Of Hypoxia On Ecm Remodelingmentioning

confidence: 61%

Influence of stress on extracellular matrix and integrin biology

et al. 2011

View full text Add to dashboard Cite

“…The ECM content, such as collagen and elastin in the walls of arteries, is increased in hypertensive patients and in genetic or experimentally-induced hypertension in animals (5,6). Many researchers have studied the mechanisms of collagen accumulation during hypertension.…”

Section: Introductionmentioning

confidence: 99%

Regulatory Effect of Hydrogen Sulfide on Vascular Collagen Content in Spontaneously Hypertensive Rats

Zhao

Zhang²,

Zhang

et al. 2008

Hypertens Res

View full text Add to dashboard Cite

show abstract

“…Total titin content is often unchanged, but the increased expression of the stiffer N2B (vs. N2BA) isoform results in higher passive myocardial stiffness (44, 45). Likewise, many chronic cardiac diseases result in an increased accumulation of interstitial collagen I and III via increased gene expression and decreased degradation (22,33). Collagen metabolism may be stimulated by hemodynamic as well hormonal factors (38,40).…”

mentioning

confidence: 99%

“…In particular, titin, a giant sarcomeric protein (9,17,18,29,43,45), and fibrillar collagen types I and III (22,32,37,40) most commonly exhibit changes that affect ventricular diastolic chamber stiffness. Recent studies in animal models of dilated cardiomyopathy and pressure overload have revealed changes in titin isoform expression that increase myocardial stiffness (44,45).…”

mentioning

confidence: 99%

Titin isoform switching is a major cardiac adaptive response in hibernating grizzly bears

Nelson

Robbins

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

The hibernation phenomenon captures biological as well as clinical interests to understand how organs adapt. Here we studied how hibernating grizzly bears (Ursus arctos horribilis) tolerate extremely low heart rates without developing cardiac chamber dilation. We evaluated cardiac filling function in unanesthetized grizzly bears by echocardiography during the active and hibernating period. Because both collagen and titin are involved in altering diastolic function, we investigated both in the myocardium of active and hibernating grizzly bears. Heart rates were reduced from 84 beats/min in active bears to 19 beats/min in hibernating bears. Diastolic volume, stroke volume, and left ventricular ejection fraction were not different. However, left ventricular muscle mass was significantly lower (300 Ϯ 12 compared with 402 Ϯ 14 g; P ϭ 0.003) in the hibernating bears, and as a result the diastolic volume-to-left ventricular muscle mass ratio was significantly greater. Early ventricular filling deceleration times (106.4 Ϯ 14 compared with 143.2 Ϯ 20 ms; P ϭ 0.002) were shorter during hibernation, suggesting increased ventricular stiffness. Restrictive pulmonary venous flow patterns supported this conclusion. Collagen type I and III comparisons did not reveal differences between the two groups of bears. In contrast, the expression of titin was altered by a significant upregulation of the stiffer N2B isoform at the expense of the more compliant N2BA isoform. The mean ratio of N2BA to N2B titin was 0.73 Ϯ 0.07 in the active bears and decreased to 0.42 Ϯ 0.03 (P ϭ 0.006) in the hibernating bears. The upregulation of stiff N2B cardiac titin is a likely explanation for the increased ventricular stiffness that was revealed by echocardiography, and we propose that it plays a role in preventing chamber dilation in hibernating grizzly bears. Thus our work identified changes in the alternative splicing of cardiac titin as a major adaptive response in hibernating grizzly bears.collagen; bradycardia; diastolic function; echocardiography MANY MAMMALS UNDERGO A UNIQUE state of energy conservation in response to harsh climatic conditions. Grizzly bears (Ursus arctos horribilis) do not eat, drink, or urinate and demonstrate minimal activity during their annual 4 -6 mo hibernation period. Cardiovascular adaptations must occur for the myocardium to remain healthy and efficient during a period of extremely low heart rates and cardiac output (6,7,8,12,26). Nonhibernators that suffer from bradycardic conditions will develop cardiac chamber dilation due to volume overload during the excessively long diastolic pauses (23,35,42). Over time, chamber dilation and elevated end-diastolic pressures lead to congestive heart failure if no intervention is sought (23, 35). However, hibernating grizzly bears tolerate extremely low heart rates without ventricular chamber dilation (30). The mechanisms that circumvent chamber dilation are not well understood, but they might involve increased ventricular stiffness (30).Molecular changes in sarcomeric and ext...

show abstract

Collagen Metabolism in Extracellular Matrix May Be Involved in Arterial Stiffness in Older Hypertensive Patients with Left Ventricular Hypertrophy

Cited by 44 publications

References 31 publications

Influence of stress on extracellular matrix and integrin biology

Influence of stress on extracellular matrix and integrin biology

Regulatory Effect of Hydrogen Sulfide on Vascular Collagen Content in Spontaneously Hypertensive Rats

Titin isoform switching is a major cardiac adaptive response in hibernating grizzly bears

Contact Info

Product

Resources

About