Effects of Compound Danshen Dripping Pills on Ventricular Remodeling and Cardiac Function after Acute Anterior Wall ST-Segment Elevation Myocardial Infarction (CODE-AAMI): Protocol for a Randomized Placebo-Controlled Trial.

BACKGROUND: Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction (AAMI) is an important factor in occurrence of heart failure which additionally results in poor prognosis. Therefore, the treatment of ventricular remodeling needs to be further optimized. Compound Danshen Dripping Pills (CDDP), a traditional Chinese medicine, exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction. OBJECTIVE: This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale. METHODS: This study is a multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The total of 268 patients with AAMI after primary percutaneous coronary intervention (pPCI) will be randomly assigned 1:1 to the CDDP group (n=134) and control group (n=134) with a follow-up of 48 weeks. Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction (STEMI), with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI, and the control group treated with a placebo simultaneously. The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI). The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide (NT-proBNP) level, arrhythmias, and cardiovascular events (death, cardiac arrest, or cardiopulmonary resuscitation, rehospitalization due to heart failure or angina pectoris, deterioration of cardiac function, and stroke). Investigators and patients are both blinded to the allocated treatment. DISCUSSION: This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI. Patients in the CDDP group will be compared with those in the control group. If certified to be effective, CDDP treatment in AAMI will probably be advised on a larger scale. (Trial registration No. NCT05000411).

Benefits of Curcumin in the Vasculature: A Therapeutic Candidate for Vascular Remodeling in Arterial Hypertension and Pulmonary Arterial Hypertension?

Growing evidence suggests that hypertension is one of the leading causes of cardiovascular morbidity and mortality since uncontrolled high blood pressure increases the risk of myocardial infarction, aortic dissection, hemorrhagic stroke, and chronic kidney disease. Impaired vascular homeostasis plays a critical role in the development of hypertension-induced vascular remodeling. Abnormal behaviors of vascular cells are not only a pathological hallmark of hypertensive vascular remodeling, but also an important pathological basis for maintaining reduced vascular compliance in hypertension. Targeting vascular remodeling represents a novel therapeutic approach in hypertension and its cardiovascular complications. Phytochemicals are emerging as candidates with therapeutic effects on numerous pathologies, including hypertension. An increasing number of studies have found that curcumin, a polyphenolic compound derived from dietary spice turmeric, holds a broad spectrum of pharmacological actions, such as antiplatelet, anticancer, anti-inflammatory, antioxidant, and antiangiogenic effects. Curcumin has been shown to prevent or treat vascular remodeling in hypertensive rodents by modulating various signaling pathways. In the present review, we attempt to focus on the current findings and molecular mechanisms of curcumin in the treatment of hypertensive vascular remodeling. In particular, adverse and inconsistent effects of curcumin, as well as some favorable pharmacokinetics or pharmacodynamics profiles in arterial hypertension will be discussed. Moreover, the recent progress in the preparation of nano-curcumins and their therapeutic potential in hypertension will be briefly recapped. The future research directions and challenges of curcumin in hypertension-related vascular remodeling are also proposed. It is foreseeable that curcumin is likely to be a therapeutic agent for hypertension and vascular remodeling going forwards.

[Chronic heart failure due to Qi deficiency and blood stasis and intervention mechanism of Compound Renshen Buqi Granules:a proteomics-based study].

Compound Renshen Buqi Granules have been widely used to treat chronic heart failure(CHF) due to Qi deficiency and blood stasis, but the mechanism of action remains unclear. This paper explored the pathogenesis of CHF due to Qi deficiency and blood stasis and the intervention mechanism of Compound Renshen Buqi Granules based on quantitative proteomics for uncovering the biological basis. SD rats were divided into the normal control(N) group, normal+Compound Renshen Buqi Granules(ND) group, model(M) group, model+Compound Renshen Buqi Granules(D) group, and positive control(Y) group. The rat model of CHF due to Qi deficiency and blood stasis was established by ligation of the left anterior descending(LAD) coronary artery and chronic sleep deprivation. The rats in the ND group and D group were provided with Compound Renshen Buqi Granules, while those in the Y group received valsartan. Six weeks later, the serum was sampled and the data-dependent acquisition(DDA) was employed for the non-targeted quantitative proteomics analysis of the differences in protein expression among groups, followed by the targeted analysis of differentially expressed proteins(DEPs) generated by data-independent acquisition(DIA). Compared with the N group, the rats in the M group pre-sented with decreased body weight, grip strength, and pulse amplitude and increased RGB value on the tongue surface. The pathomorphological examination revealed inflammatory cell infiltration, cell degeneration and necrosis, tissue fibrosis, etc. After the intervention with Compound Renshen Buqi Granules, multiple indicators were reversed. As demonstrated by proteomics results, there were 144 and 111 DEPs found in the M group and ND group in comparison with the N group. Compared with the M group, 107 and 194 DEPs were found in the D group and the Y group, respectively. Compared with the ND group, 119 DEPs were detected in the D group. As illustrated by DIA-based verification, the quantitative results of six proteins in each group were consistent with those by DDA. The syndrome indicators and pathomorphological examination results demonstrated that the protein expression profile of rats with CHF due to Qi deficiency and blood stasis changed obviously. However, Compound Renshen Buqi Granules were able to reverse the differential expression of immune proteins to regulate CHF of Qi deficiency and blood stasis syndrome, which has provided clues for figuring out the pathogenesis of CHF due to Qi deficiency and blood stasis and the intervention mechanism of Compound Renshen Buqi Granules.

Inhibitory effects of Brazilin on the vascular smooth muscle cell proliferation and migration induced by PDGF-BB.

Abnormal vascular smooth muscle cell (VSMC) proliferation and migration contribute to the pathogenesis of vascular diseases including atherosclerosis and restenosis. Brazilin isolated from the heartwood of Caesalpinia sappan L. has been reported to exhibit various biological activities, such as anti-platelet aggregation, anti-inflammation, vasorelaxation and pro-apoptosis. However, the functional effects of Brazilin on VSMCs remain unexplored. The present study investigated the potential effects of Brazilin on platelet-derived growth factor (PDGF)-BB induced VSMC proliferation and migration as well as the underlying mechanism of action. VSMC proliferation and migration were measured by Crystal Violet Staining, wound-healing and Boyden chamber assays, respectively. Cell cycle was analyzed by flow cytometry. Enzymatic action of matrix metalloproteinase-9 (MMP-9) was carried out by gelatin zymography. Expression of adhesion molecules, cell cycle regulatory proteins, the phosphorylated levels of PDGF receptor ß (PDGF-Rß), Src, extracellular signal regulated kinase (ERK) and Akt were tested by immunoblotting. The present study demonstrated that pretreatment with Brazilin dose-dependently inhibited PDGF-BB stimulated VSMC proliferation and migration, which were associated with a cell-cycle arrest at G0/G1 phase, a reduction in the adhesion molecule expression and MMP-9 activation in VSMCs. Furthermore, the increase in PDGF-Rß, Src, ERK1/2 and Akt phosphorylation induced by PDGF-BB were suppressed by Brazilin. These findings indicate that Brazilin inhibits PDGF-BB induced VSMC proliferation and migration, and the inhibitory effects of Brazilin may be associated with the blockade of PDGF-Rß - ERK1/2 and Akt signaling pathways. In conclusion, the present study implicates that Brazilin may be useful as an anti-proliferative agent for the treatment of vascular diseases.