Depressed Coronary Flow Reserve Is Associated With Decreased Myocardial Capillary Density in Patients With Heart Failure Due to Idiopathic Dilated Cardiomyopathy

Tsagalou, Eleftheria P.; Anastasiou-Nana, Maria; Agapitos, Emmanuel; Gika, Artemis; Drakos, Stavros G.; Terrovitis, John; Ntalianis, Argirios; Nanas, John N.

doi:10.1016/j.jacc.2008.05.064

Cited by 122 publications

(88 citation statements)

References 39 publications

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“…Consistent with this hypothesis are prior studies that demonstrate that administration of PDGF-BB prevents adverse remodeling after experimental myocardial infarction (38,39). More generally, our findings support the general notion that targeting cardiac angiogenesis through the PDGF/PDGFR system or via other means may be an effective approach to prevent the progression of multiple forms of heart failure (40), including "nonischemic" cardiomyopathies, in which functional and structural microvascular abnormalities are well described (41).…”

Section: Discussionsupporting

confidence: 90%

Cardiomyocyte PDGFR-β signaling is an essential component of the mouse cardiac response to load-induced stress

Chintalgattu¹,

Ai²,

Langley³

et al. 2010

J. Clin. Invest.

173

140

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PDGFR is an important target for novel anticancer therapeutics because it is overexpressed in a wide variety of malignancies. Recently, however, several anticancer drugs that inhibit PDGFR signaling have been associated with clinical heart failure. Understanding this effect of PDGFR inhibitors has been difficult because the role of PDGFR signaling in the heart remains largely unexplored. As described herein, we have found that PDGFR-β expression and activation increase dramatically in the hearts of mice exposed to load-induced cardiac stress. In mice in which Pdgfrb was knocked out in the heart in development or in adulthood, exposure to loadinduced stress resulted in cardiac dysfunction and heart failure. Mechanistically, we showed that cardiomyocyte PDGFR-β signaling plays a vital role in stress-induced cardiac angiogenesis. Specifically, we demonstrated that cardiomyocyte PDGFR-β was an essential upstream regulator of the stress-induced paracrine angiogenic capacity (the angiogenic potential) of cardiomyocytes. These results demonstrate that cardiomyocyte PDGFR-β is a regulator of the compensatory cardiac response to pressure overload-induced stress. Furthermore, our findings may provide insights into the mechanism of cardiotoxicity due to anticancer PDGFR inhibitors.

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Section: Discussionsupporting

confidence: 90%

Cardiomyocyte PDGFR-β signaling is an essential component of the mouse cardiac response to load-induced stress

Chintalgattu¹,

Ai²,

Langley³

et al. 2010

J. Clin. Invest.

173

140

View full text Add to dashboard Cite

show abstract

“…A decrease in capillary number relative to cardiomyocyte area in the heart represents an additional feature of maladaptive cardiac remodeling that is thought to contribute to the development of LV dysfunction (Tsagalou et al. 2008). We stained LV cross sections with platelet endothelial cell adhesion molecule 1 (PECAM‐1) to quantify intramyocardial capillaries relative to the cardiac myocyte area as a measurement of capillary density in the LV.…”

Section: Resultsmentioning

confidence: 99%

Endothelial mineralocorticoid receptor contributes to systolic dysfunction induced by pressure overload without modulating cardiac hypertrophy or inflammation

et al. 2017

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Heart Failure (HF) is associated with increased circulating levels of aldosterone and systemic inflammation. Mineralocorticoid receptor (MR) antagonists block aldosterone action and decrease mortality in patients with congestive HF. However, the molecular mechanisms underlying the therapeutic benefits of MR antagonists remain unclear. MR is expressed in all cell types in the heart, including the endothelial cells (EC), in which aldosterone induces the expression of intercellular adhesion molecule 1 (ICAM‐1). Recently, we reported that ICAM‐1 regulates cardiac inflammation and cardiac function in mice subjected to transverse aortic constriction (TAC). Whether MR specifically in endothelial cells (EC) contributes to the several mechanisms of pathological cardiac remodeling and cardiac dysfunction remains unclear. Basal cardiac function and LV dimensions were comparable in mice with MR selectively deleted from ECs (EC‐MR −/−) and wild‐type littermate controls (EC‐MR +/+). MR was specifically deleted in heart EC, and in EC‐containing tissues, but not in leukocytes of TAC EC‐MR −/− mice. While EC‐MR −/− TAC mice showed preserved systolic function and some alterations in the expression of fetal genes, the proinflammatory cytokine TNF α and the endothelin receptors in the LV as compared to EC‐MR +/+ TAC mice, no difference was observed between both TAC groups in overall cardiac hypertrophy, ICAM‐1 LV expression and leukocyte infiltration, cardiac fibrosis or capillary rarefaction, all hallmarks of pathological cardiac remodeling. Our data indicate that EC‐MR contributes to the transition of cardiac hypertrophy to systolic dysfunction independently of other maladaptive changes induced by LV pressure overload.

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“…This implies a decreased coronary flow reserve (greater proportion of capillaries perfused in CA hearts) (Tsagalou et al, 2008) in order to Too much cold breaks your heart! accommodate metabolic demands of the myocardium.…”

Section: Effects Of Camentioning

confidence: 99%

Cold-impaired cardiac performance in rats is only partially overcome by cold acclimation

Hui‐Kang

May

Sabharwal

et al. 2011

Journal of Experimental Biology

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SUMMARYThe consequences of acute hypothermia include impaired cardiovascular performance, ultimately leading to circulatory collapse. We examined the extent to which this results from intrinsic limitations to cardiac performance or physiological dysregulation/autonomic imbalance, and whether chronic cold exposure could ameliorate the impaired function. Wistar rats were held at a 12h:12h light:dark (L:D) photoperiod and room temperature (21°C; euthermic controls), or exposed to a simulated onset of winter in an environmental chamber by progressive acclimation to 1h:23h L:D and 4°C over 4 weeks. In vivo, acute cold exposure (core temperature, T b 25°C) resulted in hypotension (approximately -20%) due to low cardiac output (approximately -30%) accompanying a bradycardia (approximately -50%). Cold acclimation (CA) induced only partial compensation for this challenge, including increased coronary flow at T b 37°C (but not at T b 25°C), maintenance of ventricular capillarity and altered sympathovagal balance (increased low:high frequency in power spectral analysis, PSA), suggesting physiological responses alone were insufficient to maintain cardiovascular performance. However, PSA showed maintenance of cardiorespiratory coupling on acute cold exposure in both groups. Ex vivo cardiac performance revealed no change in intrinsic heart rate, but a mechanical impairment of cardiac function at low temperatures following CA. While CA involved an increased capacity for -oxidation, there was a paradoxical reduction in developed pressure as a result of adrenergic down-regulation. These data suggest that integrated plasticity is the key to cardiovascular accommodation of chronic exposure to a cold environment, but with the potential for improvement by intervention, for example with agents such as non-catecholamine inotropes. Supplementary material available online at

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Depressed Coronary Flow Reserve Is Associated With Decreased Myocardial Capillary Density in Patients With Heart Failure Due to Idiopathic Dilated Cardiomyopathy

Abstract: A marked decrease in MCD was found in patients presenting with congestive heart failure as the result of idiopathic dilated cardiomyopathy and a depressed CFR.

Cited by 122 publications

References 39 publications

Cardiomyocyte PDGFR-β signaling is an essential component of the mouse cardiac response to load-induced stress

Cardiomyocyte PDGFR-β signaling is an essential component of the mouse cardiac response to load-induced stress

Endothelial mineralocorticoid receptor contributes to systolic dysfunction induced by pressure overload without modulating cardiac hypertrophy or inflammation

Cold-impaired cardiac performance in rats is only partially overcome by cold acclimation

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