Heart - basement membrane

Research Article

Interactive relationship between basement-membrane development and sarcomerogenesis in single cardiomyocytes

Experimental Cell Research (3.905Impact Factor)

Volume 330, Issue 1, 1 January 2015, Pages 222-232

https://www.sciencedirect.com/science/article/pii/S0014482714003486?via%3Dihub

Highlights

• Development of the basement membrane network from neonatal stage to adulthood is closely related to sarcomeric formation.
• Basement-membrane laminin, sarcomeric Z-line, and transmembrane integrin all developed coordinately across a striated stage.
• The three striated structures had significant colocalizations evaluated using Pearson׳s correlation coefficients.

Abstract

The cardiac basement membrane (BM), the highly organized layer of the extracellular matrix (ECM) on the external side of the sarcolemma, is mainly composed of laminin and collagen IV, which assemble a dense, well-organized network to surround the surface of each adult cardiomyocyte. The development of the cardiac BM plays a key role in organogenesis of the myocardium through interactions between sarcomeres and integrins. Because of the complicated structure of cardiac muscle fibers and lack of a proper investigation method, the detailed interactions among BM development, sarcomeric growth, and integrin expression remain unclear. In this study, freshly isolated 3-day neonatal cardiomyocytes (CMs) were cultured on aligned collagen, which mimics the in vivo ECM structure and induces neonatal CMs to grow into rod-like shapes. Then double fluorescence-immunostained laminin and α-actinin or integrin β1 on neonatal CMs cultured 4–72 h were imaged using a confocal microscope, and the spatial relationship between laminin deposition and α-actinin expression was evaluated by colocalization analysis. At 4 h, laminin was deposited around Z-bodies (dot-shaped α-actinin) and integrins; from 18-to-72 h, its gradual colocalization with Z-lines (line-shaped α-actinin) and integrins increased Pearson׳s coefficient; this indicates that development of the BM network from the neonatal stage to adulthood is closely related to sarcomeric formation via integrin-mediated interactions.

 

 

 

Current Topics : Reviews

New Insights into the Role of Basement Membrane-Derived Matricryptins in the Heart

2017 Volume 40 Issue 12 Pages 2050-2060

DOI https://doi.org/10.1248/bpb.b17-00308

 

Abstract

The extracellular matrix (ECM), which contributes to structural homeostasis as well as to the regulation of cellular function, is enzymatically cleaved by proteases, such as matrix metalloproteinases and cathepsins, in the normal and diseased heart. During the past two decades, matricryptins have been defined as fragments of ECM with a biologically active cryptic site, namely the ‘matricryptic site,’ and their biological activities have been initially identified and clarified, including anti-angiogenic and anti-tumor effects. Thus, matricryptins are expected to be novel anti-tumor drugs, and thus widely investigated. Although there are a smaller number of studies on the expression and function of matricryptins in fields other than cancer research, some matricryptins have been recently clarified to have biological functions beyond an anti-angiogenic effect in heart. This review particularly focuses on the expression and function of basement membrane-derived matricryptins, including arresten, canstatin, tumstatin, endostatin and endorepellin, during cardiac diseases leading to heart failure such as cardiac hypertrophy and myocardial infarction.

 

Table 1. Expression and Function of Basement Membrane-Derived Matricryptins in Heart

MatricryptinsPrecursor proteinExpression and functionReferences

Arresten	Type IV collagen α1 chain	Increased expression in ischemia–reperfusion injury under mild hypothermic condition in pig	Lauten et al., 2016
Canstatin	Type IV collagen α2 chain	Decreased expression in mouse myocardial infarction model	Sugiyama et al., 2017
		Stimulation of proliferation, secretion of MMP-2 and MMP-9 and inhibition of contraction in myofibroblasts derived from rat myocardial infarction model	Sugiyama et al., 2017
		Inhibition of H2O2 apoptosis in H9c2 cardiomyoblasts	Kanazawa et al., 2017
		Stimulation of migration in rat cardiac fibroblasts	Okada et al., 2017
		Inhibition of isoproterenol-induced apoptosis in differentiated H9c2 cardiomyoblasts	Okada et al., 2016
Tumstatin	Type IV collagen α3 chain	Stimulation of proliferation and migration in rat cardiac fibroblasts	Yasuda et al., 2017b
		Inhibition of H2O2-induced apoptosis in H9c2 cardiomyoblasts	Yasuda et al., 2017a
		Decreased expression of ischemia–reperfusion injury under mild and deep hypothermic condition in pig	Lauten et al., 2016
		Increased expression of pressure-overload-induced hypertrophied myocardium in newborn rabbit	Nikolova et al., 2012
Endostatin	Type XVIII collagen α1 chain	Cardioprotective role on MCT-induced RV disease through inhibiting ICaT	Imoto et al., 2016
			Yasuda et al., 2015a
		Inhibition of bradykinin-induced mouse atrial contraction	Yasuda et al., 2015b
		Stimulation of proliferation and migration in rat cardiac fibroblasts	Okada et al., 2015
		Increased expression in pressure overload-induced mouse and newborn rabbit cardiac hypertrophy models	Givvimani et al., 2013, 2012, 2011, 2010
			Nikolova et al., 2012
		Increased expression in mouse myocardial infarction model	Qipshidze et al., 2012
		Protective role on rat myocardial infarction model	Isobe et al., 2010
		Increased expression in serum of pulmonary arterial hypertension, CHD and chronic heart failure patients	Damico et al., 2015
			Mitsuma et al., 2007
			Gouya et al., 2014
		Decreased expression in pericardial fluid of CAD patients with collaterals	Panchal et al., 2004
		No predictive information in CAD and CHD patients	Liou et al., 2006
			Eleuteri et al., 2016
			Ueland et al., 2015
Endorepellin	Perlecan domain V	Increased expression in ischemia–reperfusion injury under mild hypothermic condition in pig	Lauten et al., 2016

MMP: matrix metalloproteinase, MCT: monocrotaline, RV: right ventricular, ICaT: T-type Ca2+ channel current, CHD: coronary heart disease, CAD: coronary artery disease.

 

Impact of Ischemia-Reperfusion on Extracellular Matrix Processing and Structure of the Basement Membrane of the Heart

: deep hypothermia -> protective effect observed, basement membrane remodeling potential increased. 

(hypothermia -- high oxygen content; 

2021.08.23 - [상식+/공부자료] - 온도-용해도

Abstract

Purpose

Acute ischemic injury is a strong inductor of cardiac remodelling, resulting in structural changes of the extracellular matrix (ECM) and basement membrane (BM). In a large animal model of ischemia-reperfusion (I/R) we investigated the post-ischemic liberation of the collagen-IV-fragments Tumstatin (TUM; 28 kDa-fragment of collagen-IV-alpha-3), Arresten (ARR; 26 kDa-fragment of collagen-IV-alpha-1) and Endorepellin (LG3, 85 kDa-fragment of perlecan) which are biologically active in angiogenesis and vascularization in the post-ischemic myocardium.

Methods and Results

In this blinded study, 30 pigs were randomized to 60 min of global I/R at either 4°C or 32°C or served as control. Three transmyocardial tissue samples were collected prior to ischemia and within 30 min and 150 min of reperfusion. Tissue content of TUM, ARR and LG3 was analyzed by western blotting and immunostaining.

Within 150 min of mild hypothermic I/R a significantly increased tissue content of ARR (0.17±0.14 vs. 0.56±0.56; p = 0.001) and LG3 (1.13±0.34 vs. 2.51±1.71, p<0.001) was observed. In contrast, deep hypothermic I/R was not associated with a significant release of cleavage products. Cleavage of TUM remained unchanged irrespective of temperature. Increased matrix processing following mild hypothermia I/R is further supported by a >11fold elevation of creatine kinase (2075±2595 U/l vs. 23248±6551 U/l; p<0.001) in the coronary sinus plasma samples. Immunostaining demonstrated no changes for ARR and LG3 presentation irrespective of temperature. In contrast, TUM significantly decreased in the BM surrounding cardiomyocytes and capillaries after mild and deep hypothermic I/R, thus representing structural alterations of the BM in these groups.

Conclusion

The study demonstrates an early temperature-dependent processing of Col-IV as major component of the BM of cardiomyocytes and vascular endothelium. These observations support the protective effects of deep hypothermia during I/R. Furthermore, the results suggest an increased structural remodelling of the myocardial basement membrane with potential functional impairment during mild hypothermic I/R which may contribute to the progression to post-ischemic heart failure.