Health for Hearts United Longitudinal Trial: Improving Perceived Stress and Allostatic Load Outcomes of Mid-Life and Older African American Women.

Cardiovascular disease (CVD) continues to be the leading cause of death in the United States, with African Americans experiencing higher age-adjusted mortality compared to Whites. African American women in particular carry a high CVD burden due to more exposure to adverse personal and socioenvironmental challenges. Church-based interventions can improve health behaviors and health status of African Americans, yet few have addressed stress-related health. The purpose of this study was to determine the effectiveness of the 18-month Health for Hearts United intervention in relation to stress-related outcomes (perceived stress, allostatic load) of mid-life and older African American women (≥45 years of age; n = 152 overall sample, n = 65 clinical subsample). The results of the repeated measures analysis of variance (ANOVA) analyses showed overall significant decreases in perceived stress and allostatic load for both treatment and comparison groups over the measurement occasions (baseline and 18 months) with educational level remaining as a significant correlate over time. There was no significant interaction between treatment and time, yet there were trends in improvements for the treatment group compared to the comparison group. The findings demonstrate the potential of church-based interventions in reducing both self-reported stress and allostatic load in African American women, and highlight the need for further investigation of educational level and other possible factors influencing stress management in these settings.

Myopathy associated LDB3 mutation causes Z-disc disassembly and protein aggregation through PKCα and TSC2-mTOR downregulation.

Mechanical stress induced by contractions constantly threatens the integrity of muscle Z-disc, a crucial force-bearing structure in striated muscle. The PDZ-LIM proteins have been proposed to function as adaptors in transducing mechanical signals to preserve the Z-disc structure, however the underlying mechanisms remain poorly understood. Here, we show that LDB3, a well-characterized striated muscle PDZ-LIM protein, modulates mechanical stress signaling through interactions with the mechanosensing domain in filamin C, its chaperone HSPA8, and PKCα in the Z-disc of skeletal muscle. Studies of Ldb3Ala165Val/+ mice indicate that the myopathy-associated LDB3 p.Ala165Val mutation triggers early aggregation of filamin C and its chaperones at muscle Z-disc before aggregation of the mutant protein. The mutation causes protein aggregation and eventually Z-disc myofibrillar disruption by impairing PKCα and TSC2-mTOR, two important signaling pathways regulating protein stability and disposal of damaged cytoskeletal components at a major mechanosensor hub in the Z-disc of skeletal muscle.

Large-scale identification of human cerebrovascular proteins: Inter-tissue and intracerebral vascular protein diversity.

The human cerebrovascular system is responsible for regulating demand-dependent perfusion and maintaining the blood-brain barrier (BBB). In addition, defects in the human cerebrovasculature lead to stroke, intracerebral hemorrhage, vascular malformations, and vascular cognitive impairment. The objective of this study was to discover new proteins of the human cerebrovascular system using expression data from the Human Protein Atlas, a large-scale project which allows public access to immunohistochemical analysis of human tissues. We screened 20,158 proteins in the HPA and identified 346 expression patterns correlating to blood vessels in human brain. Independent experiments showed that 51/52 of these distributions could be experimentally replicated across different brain samples. Some proteins (40%) demonstrated endothelial cell (EC)-enriched expression, while others were expressed primarily in vascular smooth muscle cells (VSMC; 18%); 39% of these proteins were expressed in both cell types. Most brain EC markers were tissue oligospecific; that is, they were expressed in endothelia in an average of 4.8 out of 9 organs examined. Although most markers expressed in endothelial cells of the brain were present in all cerebral capillaries, a significant number (21%) were expressed only in a fraction of brain capillaries within each brain sample. Among proteins found in cerebral VSMC, virtually all were also expressed in peripheral VSMC and in non-vascular smooth muscle cells (SMC). Only one was potentially brain specific: VHL (Von Hippel-Lindau tumor suppressor). HRC (histidine rich calcium binding protein) and VHL were restricted to VSMC and not found in non-vascular tissues such as uterus or gut. In conclusion, we define a set of brain vascular proteins that could be relevant to understanding the unique physiology and pathophysiology of the human cerebrovasculature. This set of proteins defines inter-organ molecular differences in the vasculature and confirms the broad heterogeneity of vascular cells within the brain.