Inflammation and Thrombosis in Small Animal Cardiovascular Diseases—an Emerging Therapeutic Target

A special issue of Animals (ISSN 2076-2615). This special issue belongs to the section "Veterinary Clinical Studies".

Deadline for manuscript submissions: 15 May 2024 | Viewed by 3706

Special Issue Editors

Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, USA
Interests: immunothrombosis; precision medicine; platelet physiology; critical care; cardiovascular disease

E-Mail Website
Guest Editor
Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL, USA
Interests: immunothrombosis and neutrophil extracellular traps; platelet physiology; transfusion medicine; immune-mediated blood disorders

Special Issue Information

Dear Colleagues,

Thrombosis, a life-threatening complication, is a significant cause of morbidity and mortality in cardiovascular disease.  Despite this significance, its underlying pathophysiology in small animals is poorly understood. Activation of the coagulation system due to the host’s innate immunity is a normal physiologic response, known as immunothrombosis. Immunothrombosis functions to limit systemic dissemination of pathogens. The dysregulation of immunothrombosis causes a great deal of collateral damage and is characterized by overzealous activation of platelets, innate immune cells, and the coagulation system coming together in a vicious cycle of thrombosis, tissue ischemia, and excessive inflammation. Rodent models and emerging evidence in human medicine demonstrate that dysregulated immunothrombosis is associated with many cardiovascular diseases such as myocardial infarction, venous thromboembolism, pulmonary arterial hypertension, and systemic hypertension. While evidence in veterinary medicine is limited, therapeutic targets of immunothrombosis such as neutrophil extracellular traps and platelet-leukocyte interactions may hold great promise in preventing thrombotic complications of cardiovascular diseases. This Special Issue presents a collection of state-of-the-art reviews and original research articles, highlighting the interplay between inflammation and coagulation in small animals with cardiovascular diseases.

Dr. Ronald Li
Dr. Dana LeVine
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Animals is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • immunothrombosis
  • thromboinflammation
  • platelets
  • cardiomyopathy
  • auto-immune disease
  • precision medicine

Published Papers (2 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

29 pages, 5753 KiB  
Article
Multi-Omic, Histopathologic, and Clinicopathologic Effects of Once-Weekly Oral Rapamycin in a Naturally Occurring Feline Model of Hypertrophic Cardiomyopathy: A Pilot Study
by Victor N. Rivas, Joanna L. Kaplan, Susan A. Kennedy, Stuart Fitzgerald, Amanda E. Crofton, Aisling Farrell, Louise Grubb, Carina E. Jauregui, Gabriela Grigorean, Eunju Choi, Samantha P. Harris and Joshua A. Stern
Animals 2023, 13(20), 3184; https://doi.org/10.3390/ani13203184 - 12 Oct 2023
Viewed by 1449
Abstract
Hypertrophic cardiomyopathy (HCM) remains the single most common cardiomyopathy in cats, with a staggering prevalence as high as 15%. To date, little to no direct therapeutical intervention for HCM exists for veterinary patients. A previous study aimed to evaluate the effects of delayed-release [...] Read more.
Hypertrophic cardiomyopathy (HCM) remains the single most common cardiomyopathy in cats, with a staggering prevalence as high as 15%. To date, little to no direct therapeutical intervention for HCM exists for veterinary patients. A previous study aimed to evaluate the effects of delayed-release (DR) rapamycin dosing in a client-owned population of subclinical, non-obstructive, HCM-affected cats and reported that the drug was well tolerated and resulted in beneficial LV remodeling. However, the precise effects of rapamycin in the hypertrophied myocardium remain unknown. Using a feline research colony with naturally occurring hereditary HCM (n = 9), we embarked on the first-ever pilot study to examine the tissue-, urine-, and plasma-level proteomic and tissue-level transcriptomic effects of an intermittent low dose (0.15 mg/kg) and high dose (0.30 mg/kg) of DR oral rapamycin once weekly. Rapamycin remained safe and well tolerated in cats receiving both doses for eight weeks. Following repeated weekly dosing, transcriptomic differences between the low- and high-dose groups support dose-responsive suppressive effects on myocardial hypertrophy and stimulatory effects on autophagy. Differences in the myocardial proteome between treated and control cats suggest potential anti-coagulant/-thrombotic, cellular remodeling, and metabolic effects of the drug. The results of this study closely recapitulate what is observed in the human literature, and the use of rapamycin in the clinical setting as the first therapeutic agent with disease-modifying effects on HCM remains promising. The results of this study establish the need for future validation efforts that investigate the fine-scale relationship between rapamycin treatment and the most compelling gene expression and protein abundance differences reported here. Full article
Show Figures

Figure 1

12 pages, 2338 KiB  
Article
Role of Prednisolone in Platelet Activation by Inhibiting TxA2 Generation through the Regulation of cPLA2 Phosphorylation
by Sanggu Kim, Preeti Kumari Chaudhary and Soochong Kim
Animals 2023, 13(8), 1299; https://doi.org/10.3390/ani13081299 - 11 Apr 2023
Cited by 2 | Viewed by 1550
Abstract
Glucocorticoids have been commonly used in the treatment of inflammation and immune-mediated diseases in human beings and small animals such as cats and dogs. However, excessive use can lead to Cushing’s syndrome along with several thrombotic and cardiovascular diseases. Although it is well-known [...] Read more.
Glucocorticoids have been commonly used in the treatment of inflammation and immune-mediated diseases in human beings and small animals such as cats and dogs. However, excessive use can lead to Cushing’s syndrome along with several thrombotic and cardiovascular diseases. Although it is well-known that glucocorticoids exert a significant effect on coagulation, the effect of cortisol on platelet function is much less clear. Thus, we aimed to study the effects of prednisolone, one of the commonly used glucocorticoids, on the regulation of platelet function using murine platelets. We first evaluated the concentration-dependent effect of prednisolone on 2-MeSADP-induced platelet function and found that the 2-MeSADP-induced secondary wave of aggregation and dense granule secretion were completely inhibited from 500 nM prednisolone. Since 2-MeSADP-induced secretion and the resultant secondary wave of aggregation are mediated by TxA2 generation, this result suggested a role of prednisolone in platelet TxA2 generation. Consistently, prednisolone did not affect the 2-MeSADP-induced aggregation in aspirinated platelets, where the secondary wave of aggregation and secretion were blocked by eliminating the contribution of TxA2 generation by aspirin. In addition, thrombin-induced platelet aggregation and secretion were inhibited in the presence of prednisolone by inhibiting the positive-feedback effect of TxA2 generation on platelet function. Furthermore, prednisolone completely inhibited 2-MeSADP-induced TxA2 generation, confirming the role of prednisolone in TxA2 generation. Finally, Western blot analysis revealed that prednisolone significantly inhibited 2-MeSADP-induced cytosolic phospholipase A2 (cPLA2) and ERK phosphorylation in non-aspirinated platelets, while only cPLA2 phosphorylation, but not ERK phosphorylation, was significantly inhibited by prednisolone in aspirinated platelets. In conclusion, prednisolone affects platelet function by the inhibition of TxA2 generation through the regulation of cPLA2 phosphorylation, thereby shedding light on its clinical characterization and treatment efficacy in dogs with hypercortisolism in the future. Full article
Show Figures

Figure 1

Back to TopTop