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Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Chronic thromboembolic pulmonary hypertension (CTEPH) is a condition caused when pressure in small blood vessels in the lungs increases abnormally. With our company's profound expertise in CTEPH research, we are well-equipped to offer tailored solutions and comprehensive support to facilitate your research process from CTEPH therapy development to therapy commercialization.

Introduction to CTEPH

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare and potentially life-threatening condition characterized by high blood pressure in the small blood vessels of the lungs. This condition is caused by the presence of blood clots and scarring in the pulmonary arteries, leading to increased resistance to blood flow and elevated pressure within the pulmonary circulation. The incidence of CTEPH is estimated to be 5 cases per million.

The targeted therapy of chronic thromboembolic pulmonary hypertension (CTEPH). Fig. 1 Chronic thromboembolic pulmonary hypertension and targeted therapy. (Mahmud, Ehtisham, et al., 2018)

Pathogenesis of CTEPH

CTEPH is characterized by a multifaceted mechanism involving thrombosis, impaired thrombolysis, and fibrotic changes in the pulmonary arteries. It is commonly associated with incomplete resolution of acute pulmonary embolism, leading to persistent organized thrombi within the pulmonary vasculature. These retained thrombi undergo fibrotic remodeling over time, resulting in pulmonary artery stenosis and obstruction.

Pathophysiology of chronic thromboembolic pulmonary hypertension (CTEPH). Fig. 2 Pathophysiology of CTEPH. (Jung, Mi-Hyang, et al., 2022)

Targets of CTEPH Therapy

Endothelin Pathway

Endothelin-1 (ET-1) is a potent vasoconstrictor that plays a central role in regulating vascular tone and remodeling. Elevated ET-1 levels are observed in individuals with CTEPH, suggesting a role in the development of pulmonary hypertension. Endothelin receptor antagonists may serve as potential therapeutic options for CTEPH.

Nitric Oxide (NO) Pathway

Nitric oxide is a vasodilator that promotes relaxation of smooth muscle in blood vessels, thereby improving blood flow. In CTEPH, impaired NO production and signaling lead to vasoconstriction and increased pulmonary vascular resistance. NO donors or phosphodiesterase 5 inhibitors are being investigated as potential therapeutics for CTEPH.

Our Services

Drawing upon our deep expertise in biotechnology and extensive experience in the industry, our company offers all-encompassing solutions for diagnostic and therapeutic research dedicated to CTEPH.

Animal Models of CTEPH

Induced Models
Chemical induction models utilize substances that promote thrombus formation or impair thrombolysis. One such compound is monocrotaline, which is frequently used in rodent models. Monocrotaline administration leads to endothelial damage, thrombosis, and subsequent pulmonary vascular remodeling. These models help in studying the progressive fibrotic changes and hemodynamic alterations seen in CTEPH.
Genetically Engineered Models
Genetically engineered models involve the manipulation of specific genes associated with thrombosis or vascular remodeling. By targeting these genes, researchers can induce CTEPH-like phenotypes in animals. For instance, genetically modified mice with deficiencies in coagulation factors or fibrinolytic proteins have been utilized to investigate the role of these molecules in CTEPH development.
Optional Models
  • eNOS Deficiency Model
  • eNOS Mutation Model
  • SERPINE2 Overexpression Model
  • SERPINE2 Mutation Model
Surgery Models
Surgical models involve the induction of pulmonary embolism through surgical interventions. For instance, in the rat model, autologous blood clots are introduced into the pulmonary circulation, leading to the formation of organized thrombi. This approach allows researchers to mimic the persistent thrombi observed in human CTEPH individuals.
Optional Species Mice, Rats, Dogs, Pigs, Non-Human Primates (Monkeys), Others

No matter what stage of research you are at, we can provide you with corresponding research services. If you are interested in our services, please feel free to contact us for more details and quotation information for related services.

References

  • Mahmud, Ehtisham, et al. "Chronic thromboembolic pulmonary hypertension: evolving therapeutic approaches for operable and inoperable disease." Journal of the American College of Cardiology 71.21 (2018): 2468-2486.
  • Jung, Mi-Hyang, et al. "Clinical presentations and multimodal imaging diagnosis in chronic thromboembolic pulmonary hypertension." Journal of Clinical Medicine 11.22 (2022): 6678.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.

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