Cathepsin L Promotes Vascular Intimal Hyperplasia after Arterial Injury

Cai, Jingjing; Zhong, Hua; Wu, Jinze; Chen, Ruifang; Yang, Huan; Al‐Abed, Yousef; Liu, Ying; Li, Xiaohui; Jiang, Weihong; Montenegro, Marcelo F.; Yuan, Hong; Billiar, Timothy R.; Chen, Alex F.

doi:10.2119/molmed.2016.00222

Cited by 30 publications

(27 citation statements)

References 35 publications

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“…Intriguingly, all of these factors involved in the entry of SARS-CoV-2 in the host cell are known to be expressed by endothelial cells [43][44][45][46][47][48][49] (Figure 1).…”

Section: Pathogenesis Of Covid-19mentioning

confidence: 99%

Hypertension, Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an Endothelial Disease? A Comprehensive Evaluation of Clinical and Basic Evidence

Sardu

Gambardella

Morelli

et al. 2020

JCM

469

436

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The symptoms most commonly reported by patients affected by coronavirus disease (COVID-19) include cough, fever, and shortness of breath. However, other major events usually observed in COVID-19 patients (e.g., high blood pressure, arterial and venous thromboembolism, kidney disease, neurologic disorders, and diabetes mellitus) indicate that the virus is targeting the endothelium, one of the largest organs in the human body. Herein, we report a systematic and comprehensive evaluation of both clinical and preclinical evidence supporting the hypothesis that the endothelium is a key target organ in COVID-19, providing a mechanistic rationale behind its systemic manifestations.

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“…Intriguingly, all of these factors involved in the entry of SARS-CoV-2 in the host cell are known to be expressed by endothelial cells [43][44][45][46][47][48][49] (Figure 1).…”

Section: Pathogenesis Of Covid-19mentioning

confidence: 99%

Hypertension, Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an Endothelial Disease? A Comprehensive Evaluation of Clinical and Basic Evidence

Sardu

Gambardella

Morelli

et al. 2020

JCM

469

436

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“…Our pilot study demonstrates how a large-animal model is helpful in investigating the pathophysiologic process of plaques, but confirmation is needed in a small-animal model or in an in vitro study. Whether the higher expression of cathepsins in atherosclerotic plaques could contribute to the exaggerated intimal hyperplasia response seen in swine carotid arteries and models of atherosclerosis is another interesting possibility to explore in future studies [12,13].…”

Section: Discussionmentioning

confidence: 99%

“…The same operative and imaging techniques used clinically in humans can be performed in swine [10,11]. Previous studies conducted in swine show morphology and physiology of the lesions in the carotid arteries comparable to humans [12,13]. The swine model of atherosclerosis is documented as an appropriate model to investigate the pathophysiologic mechanisms leading to carotid artery atherosclerosis [14,15].…”

mentioning

confidence: 99%

Cathepsin L expression in the carotid arteries of atherosclerotic swine

Bashir

Hunter

et al. 2019

Arch Med Sci Atheroscler Dis

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Atherosclerosis is an inflammatory condition in which fatty deposits can clog the arteries and the buildups are called plaque [1]. Stroke remains a massive public health problem with tremendous health care costs. At least 20% of ischemic strokes are caused by carotid artery atherosclerotic plaque [2]. Even though there are phenomenal gains in clinical management of patients with symptomatic carotid artery disease, the molecular mechanisms and pathways leading to plaque instability remain poorly established [3,4]. Identification of the molecular markers of plaque instability along with signaling mechanisms may help in providing alternatives to surgical treatment and prevention of stroke. Cathepsin L (CTSL) is involved in inflammation and degradation of the extracellular matrix in the fibrous cap, causing destabilization of the plaque. These proteases serve as potential markers for plaque inflammation and vulnerability [5,6]. At present it is still unclear how CTSL plays a role in the development of atherosclerotic plaque instability as well as plaque rupture and necrotic core formation [7,8].A pilot study was conducted on human carotid endarterectomy tissues collected anonymously. Plaques were marked as clinically asymptomatic (A) and symptomatic (S) male and female patients, aged between 50 and 75 years. The protein expression of CTSL in S (unstable) plaques compared to A (stable) plaques were analyzed by double immunofluorescence and fibrous cap and necrotic core were assessed by morphometric analysis. Our initial findings show increased expression of CTSL in symptomatic plaques. The increased expression of CTSL in S plaques highlights the potential role of CTSL in plaque instability and needs further investigation in animal models.The porcine model is the most used and accepted model for cardiovascular diseases [9]. The same operative and imaging techniques used clinically in humans can be performed in swine [10,11]. Previous studies conducted in swine show morphology and physiology of the lesions in the carotid arteries comparable to humans [12,13]. The swine model of atherosclerosis is documented as an appropriate model to investigate the pathophysiologic mechanisms leading to carotid artery atherosclerosis [14,15]. A pilot study was conducted by us on the swine model, to further investigate the role of CTSL in the pathogenesis of carotid atherosclerosis and to enhance knowledge of the mechanistic factors and key molecules in the development of unstable plaques in vivo. To our knowledge no such study has been conducted before.

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“…Vascular cells such as vascular endothelium, and smooth muscles are important sources of Cat L [16]. Cat L promotes vascular intimal hyperplasia after arterial injury [17]. Hypertension, the most potent risk factor for CVD, can drive pathologic remodeling of the macro-and microcirculation.…”

Section: Discussionmentioning

confidence: 99%

Plasma Cathepsin L Level is Positively Associated with Arterial Stiffness in Geriatric Patients

Xu¹,

Pan²,

Chen³

et al. 2019

Artery Res

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A B S T R A C TBackground: Cathepsin L (Cat L) is involved in the regulation of vascular aging processes. The aim of this study was to evaluate the relationship between plasma Cat L level and arterial stiffness marker through brachial-ankle pulse wave velocity (baPWV) in geriatric patients. Methods:Cross-sectional study with 502 people were selected from a population of 2250 people aged over 65 years old, from three different basic health zones of Shanghai. Blood samples were collected, and the baPWV was measured with the SphygmoCor system. The geriatric patients with baPWV values >20 m/s were defined as the high arterial stiffness group.Results: In total, 248 (49.4%) of the 502 geriatric patients in this study were in the high arterial stiffness group. The high arterial stiffness group were older (p = 0.006) and had higher prevalence of hypertension (p = 0.020), coronary heart disease (CHD) (p = 0.037), higher systolic blood pressure (SBP) (p = 0.018), pulse pressure (p = 0.017), plasma Cat L (p = 0.002) and logarithmically transformed C-reactive protein (p = 0.023) levels than those in the low arterial stiffness group. Multivariable forward stepwise regression analysis showed that Cat L (b = 0.418, p = 0.011) and hypertension (b = 0.217, p = 0.029) were associated with baPWV values in geriatric patients. Moreover, an increased plasma Cat L level (odds ratio (OR): 1.048; 95% confidence interval (CI): 1.043-1.169; p = 0.018) was an independent factor for arterial stiffness among the geriatric patients. Conclusion:In this study, plasma Cat L level was positively correlated with arterial stiffness in geriatric patients.

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Cathepsin L Promotes Vascular Intimal Hyperplasia after Arterial Injury

Cited by 30 publications

References 35 publications

Hypertension, Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an Endothelial Disease? A Comprehensive Evaluation of Clinical and Basic Evidence

Hypertension, Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an Endothelial Disease? A Comprehensive Evaluation of Clinical and Basic Evidence

Cathepsin L expression in the carotid arteries of atherosclerotic swine

Plasma Cathepsin L Level is Positively Associated with Arterial Stiffness in Geriatric Patients

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