Acta physiologica (Oxford, England) · 2026
The Absence of Collagen VI Reduces Systolic Function but Paradoxically Increases Ca2+ Release in the Rat Heart.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Krstic A, Moammer H, Hassan S, Bai J, Kallingappa P, Hou Y, Annandale M, Taberner A, Han J-C, Mellor K, Ward M L, Barrett C J, Crossman D J
Аннотация
AIM: Collagen VI has recently been strongly linked to poor outcomes in heart failure through increased endotrophin, a collagen VI-derived signaling molecule linked to fibrotic remodeling in cardiovascular disease. The mutation of collagen VI can result in Ullrich congenital muscular dystrophy and Bethlem myopathy, pointing to a critical function in muscle physiology. However, the functional role of collagen VI in the heart is poorly understood. In human heart failure with reduced ejection fraction, collagen VI is increased within the remodeled T-tubules, suggesting a possible role in tubular structure and Ca2+ dynamics.
METHODS: To investigate this hypothesis, a global knockout of the collagen VI alpha 1 gene (Col6a1-/-) was generated in the rat.
RESULTS: T-tubule structure and ryanodine receptor cluster organization were unchanged, but echocardiography demonstrated reduced systolic function. Consistent with this, isolated trabeculae from Col6a1-/- hearts generated significantly less peak stress, confirming impaired contractile force at the tissue level. Paradoxically, isolated cardiomyocytes from the Col6a1-/- rat had increased Ca2+ transient amplitude and increased sarcoplasmic reticulum Ca2+ load that would be expected to increase force. β-adrenergic stimulation further increased Ca2+ transient amplitude and was associated with diastolic Ca2+ release events in Col6a1-/- cardiomyocytes. Furthermore, β-adrenergic stimulation of Col6a1-/- trabeculae exhibited spontaneous contractions, indicating an increased susceptibility to arrhythmic activity.
CONCLUSION: Together, these results indicate collagen VI has a role in both force transduction and Ca2+ cycling in the heart.
METHODS: To investigate this hypothesis, a global knockout of the collagen VI alpha 1 gene (Col6a1-/-) was generated in the rat.
RESULTS: T-tubule structure and ryanodine receptor cluster organization were unchanged, but echocardiography demonstrated reduced systolic function. Consistent with this, isolated trabeculae from Col6a1-/- hearts generated significantly less peak stress, confirming impaired contractile force at the tissue level. Paradoxically, isolated cardiomyocytes from the Col6a1-/- rat had increased Ca2+ transient amplitude and increased sarcoplasmic reticulum Ca2+ load that would be expected to increase force. β-adrenergic stimulation further increased Ca2+ transient amplitude and was associated with diastolic Ca2+ release events in Col6a1-/- cardiomyocytes. Furthermore, β-adrenergic stimulation of Col6a1-/- trabeculae exhibited spontaneous contractions, indicating an increased susceptibility to arrhythmic activity.
CONCLUSION: Together, these results indicate collagen VI has a role in both force transduction and Ca2+ cycling in the heart.