Human SERCA2a levels correlate inversely with age in senescent human myocardium

Cain, Brian S.; Meldrum, Daniel R.; Joo, Kyung Sub; Wang, Jufeng; Meng, Xianzhong; Cleveland, Joseph C.; Banerjee, Anirban; Harken, Alden H.

doi:10.1016/s0735-1097(98)00233-2

Cited by 111 publications

(65 citation statements)

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“…Reduced rates of Ca 2ϩ uptake by the sarcoplasmic reticular Ca 2ϩ pump [sarco(endo)plasmic reticulum Ca 2ϩ -ATPase (SERCA2)] during early diastole (4,12,30) and increased left ventricular stiffness, which may result from altered deposition of myocardial collagen (23,33), are likely mechanisms for the reduction in early diastolic filling that accompanies aging. In senescent rats, training increases sarcoplasmic reticular Ca 2ϩ uptake (32), attenuates the age-associated changes in collagen deposition (33), and attenuates diastolic dysfunction (2).…”

Section: Discussionmentioning

confidence: 99%

Left ventricular diastolic filling and systolic function of young and older trained and untrained men

Baldi¹,

McFarlane²,

Oxenham³

et al. 2003

Journal of Applied Physiology

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Left ventricular diastolic filling and systolic function of young and older trained and untrained men. J Appl Physiol 95: 2570-2575. First published July 25, 2003 10.1152/japplphysiol.00441.2003.-Aging is associated with impaired early diastolic filling; however, the effect of endurance training on resting diastolic function in older subjects is unclear. Heart rate and ventricular loading conditions affect mitral inflow velocities measured by Doppler echocardiography; therefore, tissue Doppler imaging of mitral annular velocity, which is relatively preload independent, was combined with mitral inflow velocity and maximal oxygen consumption (V O2 max) in young (20-35 yr) and older (60-80 yr) trained and untrained men to determine whether endurance training is associated with an attenuation of age-associated changes in diastolic filling. As expected, V O2 max was higher in trained men (P Ͻ 0.01) and lower in older men (P Ͻ 0.01). Peak early mitral inflow velocity (E) and early-to-late mitral inflow velocity ratios were lower in older vs. young men (P Ͻ 0.01); however, there was no training effect (P Ͼ 0.05). Peak early mitral annular velocity (EЈ) was higher and peak late mitral annular velocity (AЈ) was lower in young vs. older men (P Ͻ 0.01). A significant interaction effect was found for AЈ, EЈ/AЈ, and peak systolic mitral annular velocity (SЈ). Training was associated with lower AЈ in young and higher AЈ in older men. SЈ was greater in trained vs. untrained older men (P Ͻ 0.05), but it was similar in trained and untrained young men. These findings suggest that early diastolic filling is not affected by training in older men, and the effect of training on AЈ and SЈ is different in young and older men. diastolic function; aging; endurance training; maximal aerobic capacity (maximal oxygen consumption), tissue Doppler imaging AGING IS ASSOCIATED WITH AN increase in left ventricular stiffness (7), which results in a prolongation of isovolumic relaxation time (9) and incomplete relaxation of the ventricle during early diastolic filling (25). Numerous investigations have shown that peak early diastolic mitral inflow velocity (E) is reduced in aged individuals (2,10,17,18,34). To maintain ventricular filling and stroke volume, peak late diastolic filling velocity (A) increases with age (2, 17), resulting in an age-associated decline in the early-to-late mitral inflow velocity ratio (E/A) ratio (17).Aerobic fitness is associated with improved early diastolic function in young healthy subjects. Young trained athletes have increased E (20) and E/A (8, 11, 22, 26) compared with their nontrained counterparts. However, evidence to suggest that training has a similar effect in older athletes, or that training attenuates the normal age-associated decrease in E/A is inconclusive (8,10,28,31). Endurance training has been shown to improve peak filling rate in older healthy men (19), and the E/A has been shown to be higher in highly trained older endurance athletes compared with agematched healthy controls (8). However, Fleg et...

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Section: Discussionmentioning

confidence: 99%

Left ventricular diastolic filling and systolic function of young and older trained and untrained men

Baldi¹,

McFarlane²,

Oxenham³

et al. 2003

Journal of Applied Physiology

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“…23) This decrease in SERCA 2 levels was associated with impaired myocardial function at the study's baseline and further deterioration occurred during hypoxic conditions. 23) Thus, a decrease in the SERCA 2 content and the associated decrease in the SR Ca 2+ uptake have been suggested to play a major role in the diastolic dysfunction. The vulnerability of calcium reuptake is a contributing factor for the abnormal left ventricular relaxation that's been noted early in cardiac disease states, and this is despite the normal systolic function.…”

Section: )mentioning

confidence: 93%

The Pathophysiology and Diagnostic Approaches for Diastolic Left Ventricular Dysfunction: A Clinical Perspective

2005

Korean Circ J

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Heart failure with a normal ejection fraction is interchangeably termed diastolic heart failure. This condition is often unrecognized and it does have diagnostic, prognostic and therapeutic implications that are distinct from those conditions with systolic dysfunction. It is clinically important to understand and assess the diastolic function to reliably manage the patients suffering with heart failure. With the results of randomized trials for this distinct clinical syndrome, as well as the probability of better diagnostic testing in the future, physicians will in a better position not only to diagnose diastolic dysfunction or heart failure, but also to manage it more effectively. In this review, the physiology of the diastole and how to evaluate the abnormalities of the diastolic function will be discussed. EpidemiologyHeart failure is the most common hospital diagnosis for patients 65 or older at the time of discharge, and it is a major cardiovascular disorder that's still increasing in prevalence. In the early 20th century, 4% of the population reached 65 years of age; however, by the year 2010, it is predicted that 35% of the population will be older than 65 years of age.1) Cardiovascular disease is the most common cause of morbidity and mortality for the elderly. Investigators have traditionally focused on systolic functional abnormalities to explain the signs and symptoms of heart failure. However, it has become increasingly evident that diastolic functional abnormalities also play a major role for precipitating heart failure and determining the prognosis. 2-5)Four epidemiological investigations have demonstrated that nearly half of the congestive heart failure subjects in the community have normal systolic function. [6][7][8][9] Some researchers have argued that apparent "diastolic heart failure" may actually be undetected transient systolic dysfunction that is caused by an acute afterload mismatch that's induced by hypertension or this is caused by ischemia. In a recent study of 38 consecutive patients who had acute pulmonary edema and marked systolic hypertension, their heart failure was due to exacerbation of the diastolic dysfunction via hypertension, and not by transient systolic dysfunction or mitral regurgitation. 10) However, this condition, which commonly referred to as diastolic dysfunction, is often unrecognized and it does have diagnostic, prognostic and therapeutic implications that are distinct from those patients with systolic dysfunction. Thus, it is clinically important to understand and assess the diastolic function to reliably manage those patients with heart failure. In this review, we will discuss the physiology of the diastole and how to evaluate abnormalities of diastolic function. Physiology of DiastoleAbnormalities of ventricular relaxation and filling contribute to heart failure because these features result in an abnormally high ventricular diastolic pressure in relation to the diastolic volume. The most important factors that determine the relation between pressure an...

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“…18,19 Decreased SERCA and increased phospholamban may occur with ventricular hypertrophy secondary to hypertension or aortic sclerosis. 20 Ventricular hypertrophy may increase ventricular stiffness and thereby impair diastolic function. 2,3 Ventricular stiffness increases when wall thickness relative to chamber size increases.…”

Section: Pathophysiologymentioning

confidence: 99%

Diastolic Heart Failure: A Review and Primary Care Perspective

Haney

Sur²,

Xu³

2005

The Journal of the American Board of Family Medicine

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Previously the subject of much debate, there is now consensus that diastolic heart failure (DHF) represents a distinct form of heart failure. Epidemiologic data indicate that DHF is common. Indeed, there is evidence that, among elderly persons, DHF is more common than systolic heart failure (SHF). Like SHF, DHF is associated with significant morbidity, mortality, and cost; however, few clinical trials focusing on isolated DHF have been completed. Much of the treatment of DHF is based on current concepts of the pathophysiology of DHF, small clinical studies, and experience gained from treating patients with SHF. The diagnosis of DHF is clinical; data supporting the establishment of a diagnosis of DHF are limited. Differences exist in prognosis and treatment between diastolic and systolic heart failure. This article reviews diastolic heart failure with emphasis on evidence-based management, aimed at primary care physicians who routinely provide care to patients with DHF. (J Am Board Fam Pract 2005;18:189 -98.)

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Human SERCA2a levels correlate inversely with age in senescent human myocardium

Abstract: Senescent human myocardium exhibits decreased myocardial SERCA2a content with age, which may, in part, explain impaired myocardial function after either I/R or Ca2+ exposure.

Cited by 111 publications

References 58 publications

Left ventricular diastolic filling and systolic function of young and older trained and untrained men

Left ventricular diastolic filling and systolic function of young and older trained and untrained men

The Pathophysiology and Diagnostic Approaches for Diastolic Left Ventricular Dysfunction: A Clinical Perspective

Diastolic Heart Failure: A Review and Primary Care Perspective

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