Plasma Kallikrein Inhibitors in Cardiovascular Disease

Kolte, Dhaval; Shariat‐Madar, Zia

doi:10.1097/crd.0000000000000069

Cited by 33 publications

(23 citation statements)

References 143 publications

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“…Numerous monomers of black tea TFs, especially TF3, reduce the lipid deposition in hepatic cells by activating the AMPK signaling pathway to prevent NAFLD by preventing prekallikrein (PK) biosynthesis and release. PK is a trypsin-related serine protease produced during proteolytic degradation of prekallikrein by the factor-XII, prolyl carboxypeptidase (PRCP), or certain intrinsic or extrinsic stimuli [ 54 ]. The pharmacological examinations highlighted that the downregulation of PK is linked with anti-inflammatory responses, controlling hypertension, recovery in cardiovascular issues, hemostasis, and improvement in metabolic activities [ 55 ].…”

Section: Health Effects Of Tfsmentioning

confidence: 99%

[Retracted] Theaflavin Chemistry and Its Health Benefits

Shan

Nisar

et al. 2021

Oxidative Medicine and Cellular Longevity

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Huge epidemiological and clinical studies have confirmed that black tea is a rich source of health-promoting ingredients, such as catechins and theaflavins (TFs). Furthermore, TF derivatives mainly include theaflavin (TF1), theaflavin-3-gallate (TF2A), theaflavin-3 ′ -gallate (TF2B), and theaflavin-3,3 ′ -digallate (TF3). All of these TFs exhibit extensive usages in pharmaceutics, foods, and traditional medication systems. Various indepth studies reported that how TFs modulates health effects in cellular and molecular mechanisms. The available literature regarding the pharmacological activities of TFs has revealed that TF3 has remarkable anti-inflammatory, antioxidant, anticancer, antiobesity, antiosteoporotic, and antimicrobial properties, thus posing significant effects on human health. The current manuscript summarizes both the chemistry and various pharmacological effects of TFs on human health, lifestyle or aging associated diseases, and populations of gut microbiota. Furthermore, the biological potential of TFs has also been focused to provide a deeper understanding of its mechanism of action.

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Section: Health Effects Of Tfsmentioning

confidence: 99%

[Retracted] Theaflavin Chemistry and Its Health Benefits

Shan

Nisar

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…Therefore, kallikreins are considered as attractive targets for the development of novel therapies for airway disorders (39), cardiovascular disease (40), brain injury (41), skin inflammation and allergy (42) and neoplastic disorders (43). Increasing evidence indicates that many kallikreins are implicated in carcinogenesis (44) and are utilized as potential biomarkers for head and neck squamous cell carcinoma (45) and colorectal adenocarcinoma (46).…”

Section: Discussionmentioning

confidence: 99%

Transcriptome reveals the overexpression of a kallikrein gene cluster (KLK1/3/7/8/12) in the Tibetans with high altitude-associated polycythemia

Gesang

Zhang

et al. 2016

International Journal of Molecular Medicine

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High altitude-associated polycythemia (HAPC) is a very common disease. However, it the disease is still unmanageable and the related molecular mechanisms remain largely unclear. In the present study, we aimed to explore the molecular mechanisms responsible for the development of HAPC using transcriptome analysis. Transcriptome analysis was conducted in 3 pairs of gastric mucosa tissues from patients with HAPC and healthy residents at a similar altitude. Endoscopy and histopathological analyses were used to examine the injury to gastric tissues. Molecular remodeling was performed for the interaction between different KLK members and cholesterol. HAPC was found to lead to morphological changes and pathological damage to the gastric mucosa of patients. A total of 10,304 differentially expressed genes (DEGs) were identified. Among these genes, 4,941 DEGs were upregulated, while 5,363 DEGs were downregulated in the patients with HAPC (fold change ≥2, P<0.01 and FDR <0.01). In particular, the kallikrein gene cluster (KLK1/3/7/8/12) was upregulated >17-fold. All the members had high-score binding cholesterol, particularly for the polymers of KLK7. The kallikrein gene cluster (KLK1/3/7/8/12) is on chromosome 19q13.3–13.4. The elevated levels of KLK1, KLK3, KLK7, KLK8 and KLK12 may be closely associated with the hypertension, inflammation, obesity and other gastric injuries associated with polycythemia. The interaction of KLKs and cholesterol maybe play an important role in the development of hypertension. The findings of the present study revealed that HAPC induces gastric injury by upregulating the kallikrein gene cluster (KLK1/3/7/8/12), which can bind cholesterol and result in kallikrein hypertension. These findings provide some basic information for understanding the molecular mechanisms responsible for HAPC and HAPC-related diseases.

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“…The N terminal region of PK consists of four contagious repeats composed of 4 groups of 90-91 amino acids arranged in 'apple domains' (A1-A4), Figure 1. The N-terminal of the PK lacks intrinsic activity and mainly involved in the recruitment of certain proteins [33]. The majority of PK circulates in plasma as a complex with alpha globulin, high molecular weight kininogen (HK).…”

Section: Plasma Kallikreinmentioning

confidence: 99%

Investigational plasma kallikrein inhibitors for the treatment of diabetic macular edema: an expert assessment

Bhatwadekar

Kansara

Ciulla

2020

Expert Opinion on Investigational Drugs

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Introduction: Plasma kallikrein is a mediator of vascular leakage and inflammation. Activation of plasma kallikrein can induce features of diabetic macular edema (DME) in preclinical models. Human vitreous shows elevated plasma kallikrein levels in patients with DME. Because of the incomplete response of some patients to anti-VEGF agents, and the treatment burden associated with frequent dosing, there is still considerable need for VEGF-independent targeted pathways. Areas covered: This review covers the role of plasma kallikrein in the pathogenesis of DME and the therapeutic potential of plasma kallikrein inhibitors. It discusses early clinical studies of plasma kallikrein pathway modulation for DME, which have been associated with some improvement in visual acuity but with limited improvement in macular edema. This review also highlights KVD001, which is furthest along the development pathway, THR-149, which has recently completed a phase 1 study, and oral agents under development. Expert opinion: Plasma kallikrein inhibitors have a potential role in the treatment of DME, with mixed functional/anatomic results in early clinical trials. Given the large unmet need in DME treatment, further studies are warranted.

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Plasma Kallikrein Inhibitors in Cardiovascular Disease

Cited by 33 publications

References 143 publications

[Retracted] Theaflavin Chemistry and Its Health Benefits

[Retracted] Theaflavin Chemistry and Its Health Benefits

Transcriptome reveals the overexpression of a kallikrein gene cluster (KLK1/3/7/8/12) in the Tibetans with high altitude-associated polycythemia

Investigational plasma kallikrein inhibitors for the treatment of diabetic macular edema: an expert assessment

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